Department of Clinical Physiology, Nuclear Medicine &

Department of Clinical Physiology, Nuclear Medicine & PET Annual Report 2015

Rigshospitalet · University of Copenhagen Contents

Mission and objectives...... 5 Organisation and Staff 2015...... 6 Medical Secretaries...... 11 Highlights...... 12 Nuclear Medicine ...... 14 Clinical physiology and nuclear medicine ...... 16 Radionuclide monitoring of leakage during hyperthermic isolated limb perfusion...... 18 Paediatric Nuclear Medicine...... 20 Cardiac 82Rb-PET/CT ...... 22 Nuclear medicine technologists, radiographers and lab technicians...... 26 PET and PET hybrid systems...... 30 Cyclotron unit...... 32 Radiochemistry...... 36 PET/CT in Oncology, Infection and Inflammation...... 40 PET/CT- scanning in Radiation Therapy...... 42 Clinical PET scanning of the brain...... 44 Rigshospitalet PET/MR...... 46 King Frederik V founded Rigshospitalet in 1757. Today, it has 1,200 beds and 12,000 employees. Magnetic Resonance Imaging provides clinical physiological information ...... 48 Research at Rigshospitalet is published in more than 2,000 peer review papers per year, including 64Cu-DOTA-AE105 PET ...... 50 higher academic theses (PhD and Doctor of Medical Science). Rigshospitalet is part of The Capital Academic and other activities...... 51 Region of Denmark and is a Copenhagen University Hospital. Studies 2015...... 54 Finance...... 57 Glostrup Hospital Equipment 2015...... 58 Glostrup Hospital were established in 1958, and 1st of January 2015 Rigshospitalet, Blegdamsvej and Publications 2015...... 60 Glostrup Hospital were unified as Rigshospitalet. SpinLab MR Hyperpolarizer...... 68 HyperPET...... 70 University of Copenhagen Research...... 72 The University of Copenhagen was founded in 1479. The Faculty of Health and Medical Sciences BIIC...... 75 has 10,000 students, including medicine and bioengineering in collaboration with The Technical Cluster for Molecular Imaging...... 76 University of Denmark, DTU. The University of Copenhagen is member of IARU, The International Collaboration with Landssygehuset, Faroe Islands...... 78 Alliance of Research Universities. www.ku.dk Danish-Chinese and Danish-Indian Research ...... 80 PhD degree in medical and molecular imaging...... 82 Global Academic Program...... 83 Young Investigator Prizes...... 84 64Cu-DOTATATE PET...... 85 CIMBI...... 86 MSc in Medicine and Technology...... 88 Danish National Research Foundation...... 90 Accreditation...... 92 Preface

2015 was a year with New Beginnings: Rigshospitalet, Blegdamsvej and ical Physiology Rigshospitalet Blegdamsvej, and the little unit Biolab To all the other researchers in the department we would like to say Thank you to our directors at the Center of Diagnostics, Rigshospitalet, Glostrup Hospital were unified to one big hospital, and the Departments with assays for special biochemistry analyses has been placed in the big the same thank you and honors for a fine effort. Professor Ian Law Center Director Bettina Lundgren, MD DMSc and Vice Director Lene of Clinicial Physiology and Nuclear Medicine were unified to one big new Department of Clinical Biochemistry, as the professional and scien- has established his one-stop-shop PET/MR for diagnosis of patients Ørnstrup and their team for important positive and helpful collabora- department with sections both in Glostrup and Rigshospitalet, Bleg- tific competences belong there. with dementia and brain tumors, Consultant Lise Borgwardt has es- tion. Thank you to Department of Radiology, Head of Department Ilse damsvej. The leadership of the department is Heads of Department, tablished the paediatric program with now 3.000 paediatric patient Vejborg and Chief Radiographer Johnny Madelung for positive collabo- Professor Liselotte Højgaard and Chief Technologist Linda M. Kragh. FIU, the Unit for Functional Imaging, with high profile MRI investiga- investigations 2015, Consultant Jann Mortensen has extended his ration in the unification process. tions and research of brain and heart is now part of the Department of comprehensive program in lung physiology and nuclear medicine, The unification has been a positive process with a lot of work for every- Clinical Physiology, Nuclear Medicine and PET, and we are proud to Consultant Annika Loft Jakobsen has extended the comprehensive Our aim is to deliver the best patient treatment and the best research and one in terms of organisation, administration and economy, but it has had welcome the fine research group lead by Professor Henrik Larsson. program on PET/CT for clinical oncology, Consultant Philip Hasbak education. Thank you to all staff, collaborators and international col- a positive synergistic effect for research, clinical patient investigations has established the cardiology research program with Rubidum-PET, leagues for making this possible. and education. We established a teleconference facility at both addresses The section in Glostrup is, as can be seen from our organisational dia- Consultant Peter Oturai has, together with Jann Mortensen, devel- and staff meetings, clinical conferences and presentations can be held gram, 1 of 5 sections in the department, and it is led by Consultant oped the neuroendocrine tumor clinical program with now 100 patient with participants at the same time in Glostrup and Blegdamsvej. We are Peter Hovind and Staff Technologist Lis Larsen. We look forward to the treatments per year and Consultant Johan Löfgren has struggled very now a department with more than 240 employees, a big and busy clini- benefits of the full implementation here in 2016 and onward, and we hard and made a big effort to secure the ICT in spite of a lousy per- cal everyday practise at Blegdamsvej with over 100.000 investigations anticipate a growing and strengthened program in clinical patient formance of the PACS system in the hospital. To Consultant Malene per year and in Glostrup more than 20.000 per year. studies, research and education and PET/CT for 2016. Fischer honors for a research program in collaboration with your associate professorship. Researchwise Blegdamsvej published about 130 peer review publica- The research has been a tremendous success in 2015 with Professor tions and theses in 2015 and Glostrup about 35. Compared to the size Andreas Kjær at the helmet as responsible for research at the unified Thank you to Chief Production Manager, Chemist Jacob Madsen and of the sections it is for both very successful results, and we are well on department. Andreas Kjær has had success himself personally with big Chief Radiochemist Nic Gillings for an exquisite radiochemistry unit, track for our goal: To be one of the five leading departments in our area grants from Danish and international foundations with the ERC Ad- to Chief Cyclotron Physicist Holger Jensen and Cyclotron Physicist in 2020 on an international scale. vanced Grant as the most exquisite. We are privileged to house his com- Jesper Jørgensen for the cyclotron productions from the two in house Liselotte Højgaard Linda M. Kragh prehensive program of molecular imaging and look very much forward cyclotrons. To the team of physicists and computerscientist: Søren Holm, Professor, Head of Department Chief Technologist The Section in Glostrup was part of Diagnostic Department with radi- to follow the development of the uPAR tracer for grading of invasive- Thomas Levin Klausen, Bryan Haddock, Flemming Andersen and their ology, clinical physiology, nuclear medicine and clinical biochemistry in ness and malignancy in non-invasive PET/CT scanning. team, thank you for making it all work - together with your own fine one unit. Now Clinical Physiology from Glostrup is together with Clin- research production.

2 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 3 Mission and objectives

The mission of Rigshospitalet is to be the leading The objectives of the Department of Clinical Physiology, hospital in Denmark for patients in need of highly Nuclear Medicine & PET are: specialized treatment. » to provide optimal clinical physiology and nuclear medicine for patient investigations and patient The general objectives of Rigshospitalet are: treatment with radiopharmaceuticals » to be at the forefront of highly specialized diagnostic » to carry out research at the highest international level treatment and nursing in clinical physiology and nuclear medicine with » to carry out research and development at an advanced special emphasis on molecular imaging, isotopes and international level radiopharmaceuticals » to educate staff in the health services to a highly » to deliver undergraduate and postgraduate education for specialized level all relevant professionals nationally and internationally » to contribute with professional advice and exchange » to provide a good patient experience and ensure the of knowledge and expertise to the wider healthcare wellbeing of patients, relatives and staff community » to be characterized by openness and human respect We aim high – we strive to be one of the five best departments of this kind world wide before 2020.

The staff participates in many congresses, symposias, meetings and workshops with invited lectures, oral presentations, abstracts and posters. We have a comprehensive program for all staff members at the department, and frequent visits from Danish and international research groups.

4 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 5 Abrahamsson, Elisabeth, Radiographer. Christensen, Kirstine Kjær, Student. Grave, Tine, Medical Secretary. Agner, Elissaveta Castella, Radiographer. Christensen, Thomas Emil, MD, PhD Student. Gutt, Lars Emil, Student. Organisation and Staff 2015 Albers, Mia C. Hjorth, Teaching NMT. Christensen, Tine Nøhr, MD, PhD Student. Haddock, Bryan Thomas, Chief Physicist. Albrecht-Beste, Elisabeth, MD, Consultant. Clausen, Malene Martini, MD, PhD, Postdoc. Hag, Anne Mette Fisker, MSc Human Biology, Alslev, Louise, MD, Staff Specialist. Clemmensen, Andreas Ettrup, MSc Med.Tech, PhD, Postdoc, Research Coordinator. Al-Tai, Reya Tarik Hamid, NMT. PhD Student. Hansen, Adam Espe, Physicist. Amtoft, Annemarie Gjelstrup, MD, Consultant. Cortsen, Annette, NMT. Hansen, Anders Elias, DVM, PhD, Postdoc. Anderberg, Lasse, Student. Costa, Junia, MD, Staff Specialist. Hansen, Anja Vallin, NMT, Clinical Instructor. Andersen, Anne Sofie Bech, Student. Cramer, Stig Præstekjær, MD, PhD, Postdoc. Hansen, Camilla Josephine Teglgaard, NMT. Andersen, Flemming, MSc, PhD, Chief Computer Dahan, Daniel, Cyclotron Technician. Hansen, Casper, Student. Scientist. Dähnhardt, Andreas, Computer Assistant. Hansen, Christian, Student. Andersen, Julie Bjerglund, MD, PhD Student. Dall, Bente, NMT. Hansen, Lasse, NMT, Clinical Instructor. Andersen, Kim Francis, MD, Staff Specialist. Damgaard, Jeannette, Radiographer. Hansen, Matilde Bro, Student. Andersen, Ulrik Bjørn, MD, Consultant. de Nijs, Robin, Med. Physicist, MSc, PDEng, PhD. Hansen, Michele Zaugg, Student. Anthony, Erwin Jørry, Cyclotron Technician. Dejanovic, Danijela, Staff Specialist. Hansen, Ole Michael Raun, NMT. Azizi, Nadia, Radiographer. Denholt, Charlotte Lund, MSc, PhD, Chemist. Hansen, Rie Beck, Student. Barløse, Mads Christian Johannes, MD, Registrar. Do, Manh Tan, Student. Harder, Fie Barbara, NMT. Belmouhand, Mohamed, Scholarship. Døssing, Kristina Benedikte Vangsted, MSc Hasbak, Philip, MD, Consultant. Benjaminsen, Claus, MSc Engineer. Biology, PhD Student. Hasler, Signe Winther, Student. Benoit, Didier, Physicist, Postdoc. Drachmann, Anders Paaske, Student. Hassan, Mariam, NMT. Benzon, Eric von, MD, Consultant. Dunbar, Douglas, NMT. Hassing, Christina, Student. Berg, Ronan Martin Griffin, MD, Registrar. El-Ali, Henrik Hussein, Physicist, PhD, Ass. Prof. Henriksen, Frederik Hurup, Student. Berthelsen, Anne Kiil, MD, Consultant. Elkington, Sakeena, NMT. Henriksen, Otto Mølby, MD, PhD, Consultant. Binderup, Tina, MSc Human Biology, PhD, Ellebæk, Sofie, MSc Biotech, PhD Student. Hercman, Alexandra Regina Nowacka, NMT. Postdoc. Ellegaard, Andreas Høyby, Student. Hildebrand, Sanne, Secretary. Birch, Kirsten Junker, NMT. Enevoldsen, Lotte Hahn, MD, Consultant. Hirsi, Abdi Hafied, Registrar. Bisgaard, Sissel, Student. Engberg, Astrid, Student. Højgaard, Liselotte, MD, DMSc, Professor, Head Borgwardt, Henrik Gutte, MD, PhD, Postdoc. Federspiel, Marianne, NMT. of Department. Borgwardt, Lise, MD, PhD, Consultant. Fischer, Barbara Malene, MD, DMSc, PhD, Holm, Søren, MSc, PhD, Chief Physicist. Børresen, Betina, DVM, PhD Student. Consultant. Holm, Stine, NMT. Brandt-Larsen, Malene, MSc, PhD, Chemist. Fishekxhiu, Elida Sinik, NMT. Holten, Victoria, Student. Brittain, Jane Maestri, MD, Senior Registrar. Fliedner, Frederikke Petrine, Research Assistant. Holtz, Simon Herken, MSc, QA Academic. Brogaard, Rikke Yding, MSc Engineer, PhD Foldager, Annette, Teaching NMT. Hovind, Peter, MD, DMSc, Consultant. Student. Folkmann, Nanna Freja, Secretary. Hurry, Preetee Kapisha, Senior Registrar. Buhelt, Sophie, Student. Fosbøl, Marie Øbro, MD, Senior Registrar. Iljazovska, Cejlan Zulfovska, NMT. Cappelen, Anna, Student Frederiksen, Mette, NMT. Ismaili Abd, Schorlarship. Cappelen, Katrine Louise, Engineer. Frost, Nadia, Student. Jakobsen, Annika Loft, MD, PhD, Consultant. Choudry, Aisha Bilal, Student. Frydendahl, Christina Schjøth, MSc Chem, PhD, Jensen, Berit, NMT. Christensen, Anders, MD, PhD Student. Postdoc. Jensen, Holger, MSc, PhD, Chief Cyclotron Christensen, Camilla, Chemist. Fuchs, Annette, Scholarship. Physicist. Christensen, Camilla, NMT. Gelle, Liibaan Mohamed, NMT. Jensen, Irene Cecilie, Student. Christensen, Charlotte Birk, MD, Staff Specialist. Ghotbi, Adam Ali, MD, PhD Student. Jensen, Julie Milbak, Student. Christensen, Helle, NMT and Nurse. Gillings, Nicholas, MSc, PhD, Chief Radiochemist. Jensen, Line Due, Radiographer. Christensen, Jan Damgaard, Cyclotron Technician. Girkov, Mia Seremet, Scholarship. Jensen, Martin Juul Ravn, NMT.

6 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 7 Jensen, Mathilde Daniele Ørbæk, Scholarship. Lærke, Sonja Pedersen, Technician. Myltoft, Mette Gylling, Medical Secretary. Jensen, Mathilde Dyrholm, Student. Langer, Jonathan Andreas Wang, Student. Myschetzky, Rebecca Sue Main, NMT. Jensen, Mette Munk, MSc Human Biology, PhD, Langer, Natasha Hemicke, Scholarship. Nedergaard, Mette Kjølhede, MD, PhD, Postdoc. Postdoc. Larsen, Anne Fensløv, Student. Nehme, Ghina, NMT. Jensen, Rasmus Ramsbøl, MSc Engineer, PhD. Larsen, Christina Vang, NMT. Nielsen, Anders Bo, Student. Jensen, Tina Gade, QA Assistant. Larsen, Lis, Staff Technologist. Nielsen, Carsten Haagen, MSc Med.Tech, Jeppesen, Troels Elmer, Chemist, PhD Student. Larsen, Trine Bjørnbo, MSc Pharm Tech, PhD Student. Johannesen, Helle Hjorth, MD, Consultant. Phd Student. Nielsen, Cora Schaumann, NMT. Johnbeck, Camilla Bardram, MD, PhD Student. Larsson, Henrik Bo Wiberg, MD, DMSc, Nielsen, Dorthe Baunbjerg, NMT. Jørgensen, Annegrethe, NMT. Consultant, Professor. Nielsen, Kirstine, Student. Jørgensen, Jennifer Solgaard, MSc Engineer Lass, Jakob, Student. Nielsen, Mariane, Service Assistant. Biotech, PhD Student. Laugesen, Monika, Student. Nielsen, Tina Vikmann, Medical Secretary. Jørgensen, Jesper Tranekjær, MSc Human Biology, Law, Ian, MD, PhD, Consultant, Professor. Nørgaard, Martin, Engineer. PhD, Postdoc. Lehel, Szabolcs, MSc, PhD, Chemist. Nørregaard, Kamilla, MSc Physicist, PhD, Postdoc. Jørgensen, Jesper, MSc, Cyclotron Physicist. Li, Fan, MSc Med Tech, PhD, Postdoc. Nørst, Tim Niclas, NMT. Jørgensen, Louise, MD, Research Assistant. Lindberg, Ulrich, MSc. Engineer, PhD. Nyrnberg, David Enslev, Student. Jørgensen, Mette Møller, NMT. Lindell, Elin, NMT. Olesen, Oline Vinter, MSc Engineer, PhD. Juhl, Karina, MSc Human Biology, PhD Student. Linnet, Solveig, NMT. Olin, Anders. Student. Juul, Christian Ammitzbøll, MSc Biology, Ljunggren, Anna, NMT. Olsen, Ingrid Marie Holst, MD, PhD, Postdoc. PhD Student. Löfgren, Johan, MD, Consultant. Olsen, Paw Winther, Engineer. Kaijer, Michelle Nymann, Technologist, PA Ludvig, Helle, NMT. Omanovic, Dzenita, Student. Professor Andreas Kjær. Lundberg, Helena Inez Sofia, MD, Registrar. Ørting, Silas, Student. Karnov, Kirstine, MD, PhD Student. Lundby, Tim Mølgaard, Staff Technologist. Østergaard, Daniella Elisabet, Scholarship. Rasmussen, Thomas, MD, PhD, Postdoc. Skovgaard, Dorthe Charlotte, MD, PhD, Postdoc. Wikke, Tina, NMT. Keller, Sune Høgild, MSc, PhD, Computer Scientist. Lundsgaard, Christoffer Cramer, Student. Østrem, Ragnhild Garborg, MSc Nanosci, Rexhepi, Lume, NMT. Sommer, Niyan, NMT. Wittekind, Anne-Mette Nielsen, QA Pharmacist. Kielsgaard, Kathrine, Student. Madsen, Casper Lillegård, Student. PhD Student. Ripa, Rasmus Sejersten, MD, DMSc, Staff Specialist. Sørensen, Anne, Staff Technologist. Wrang, Helene, NMT. Kjær, Andreas, MD, DMSc, PhD, MBA, Madsen, Jacob, MSc, PhD, Chemist, Oturai, Peter, MD, Consultant. Risør, Louise Madeleine, Registrar. Sørensen, Jette Bitten, Service Assistant Yerst, Joo Lærke, NMT. Consultant, Professor. Chief Production Manager. Oxbøl, Jytte, Chief Technologist. Rømer, Maria Unni Koefoed, MD, PhD, Registrar. Sørensen, Louise Lendorf Sørup, NMT. Zarnani, Kiyana, PhD Student. Kjær, Kristian Skov, Student. Madsen, Lasse Ahlbech, Student. Pedersen, Kate, Staff Technologist. Rønbirk, Lilian, Medical Secretary. Stahlfest, Marianne, Medical Secretary. Zornhagen, Kamilla Westarp, DVM, PhD Student. Klausen, Thomas Levin, MSc, Chief Physicist. Magnusson, Linda Helena Margaretha, Pedersen, Kirsten Foldberg, Radiographer. Rønn, Vibeke, Head Medical Secretary, Stahr, Karin, NMT. Aagaard, Christina Byrne Faurholt, MD, Kleczewski, Karina, Medical Secretary. Technologist. Pedersen, Maria Badir, Student. PA Professor Liselotte Højgaard. Suetta, Charlotte Arneboe, MD, PhD, Consultant, PhD Student. Klyver, Cecilia, Student. Malmberg, Catarina Anna Evelina, Scholarship. Pedersen, Sune Folke, MSc Human Biology, Rønne, Frederik Malmborg, MD, Ass. Professor. Knigge, Pauline Natalie Seindal, Student. Mark, Peter Dall, Student. PhD, Postdoc. Senior Registrar. Svalling, Susanne, NMT. Knudsen, Camilla Sloth, NMT. Marner, Lisbeth, MD, DMSc, PhD, Staff Specialist. Pejtersen, Maria, NMT. Rosiek, Christian Anker, Student. Svendsen, Nini Hvidtfeldt, NMT. Knudsen, Jesper Andreas, MD, PhD, Post doc. Martín, Marina Simón, Student. Petersen, Lars Ringgaard, MSc Bio.Med, Rostrup, Egill, MD, DMSc, Consultant. Teksen, Alime Sema, Student. Korsholm, Kirsten, MD, Senior Registrar. Mehlsen, Anne-Birgitte, Consultant. PhD Student. Salihu, Armend, NMT. Therkildsen, Pia, Secretary. Kragh, Linda M., Chief NMT. Mikkelsen, Mathias, Student. Petersen, Lotte Pia, Service Assistant. Saxtoft, Eunice, NMT, Clinical Instructor. Tolstrup, Britt Maria Jæger, Radiographer. Kristensen, Lotte Kellemann, MSc Human Mistry, Jacqueline Møller, Student. Philipsen, Frederik Ersø, Student. Schou, Mikkel, Student. Tønnesen, Rune, MD, PhD Student. Biology, Research Assistant. Mohebi, Ali, Student. Porojan, Monica, Technician. Schou, Peter, Cyclotron Technician. Vensby, Philip Hvalsøe, Registrar. Kristiansen, Jonas Frimer, Student. Mølvig, Bjørn Hübschmann, Student. Poulsen, Constance Eline Grandjean, Student. Schulze, Christina, NMT. Vestergaard, Mark Bitch, PhD Student. Krogager, Louise, Student. Mortensen, Jann, MD, DMSc, Consultant, Poulsen, Jákup Martin, Radiographer. Semitoje, Gudrun, Medical Secretary. Vignisdottir, Lilja Dögg, Radiographer. Kronvall, Johanna, NMT. Ass. Professor. Pourhassan, Houman, MSc Bio.Chem, PhD Student. Setterberg, Victoria, NMT. Vinther, Johanne Constance Ilve, la Cour, Jeppe Lerche, MD, PhD Student. Mose, Camilla, NMT. Raghava, Jayachandra Mitta, MSc, Postdoc. Simonsen, Helle Juhl, NMT. Management Secretary. Ladefoged, Claes Nøhr, Computer Scientist, PhD Mottelson, Mathis Nygaard, Student. Rahbek, Rikke Sofie, Student. Skou, Katrine Bugge, MSc Med.Tech, Weihrauch, Per, Cyclotron Technician. Student. Munkholm-Larsen, Mathias, Student. Rasmussen, Sine Hvid, Scholarship. Research Assistant. Weihrauch, Simone, Student.

8 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 9 Medical secretaries

In PET, in KF and in Glostrup we have our Mette Gylling Myltoft, Medical Secretary Lilian highly competent secretaries extremely impor- Rønbirk, Medical Secretary Marianne Stahlfest, tant for referral of patients, organisation of the Secretary Sanne Hildebrand, Medical Secretary flow of patients through the department, writ- Karina Kleczewski, Medical Secretary Tine ing the reports and sending them to the depart- Grave, Management Secretary Johanne Vinther, ments. They do a very dedicated effort so that Secretary Nanna Folkmann and Secretary Pia we have no waiting lists for the patients or for Therkildsen. the reports. In all three sections we have been challenged by staff members who have been ill Our Chief Medical Secretary Vibeke Rønn is for longer periods, but in spite of that the teams assistant to the Heads of Department and is have performed brilliantly. They master the also a great help in the daily work, when it is complicated booking and secure that the wait- needed. ing lists, the patient control examinations and research scans can be done in spite of the very We would like to say a warm thank you to high work load. A dedicated thank you to Med- everyone for the high performance. ical Secretary Tina Vikmann Nielsen, Medical Secretary Gudrun Semitoje, Medical Secretary

10 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 11 Highlights Nuclear Medicine Technologist Joo Lærker Yerst volunteered in Sierra Leone for the Ebola battle. Patient no 200 for Radium-223 We are all very impressed by Joo’s contribution to world health treatment was celebrated to Professor Andreas expres gratitude to our Kjær received an dedicated staff ERC Advanced Grant summer 2015. The department is very proud of this.

The Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet was unified with the A figure Clinical Physiology and Nuclear Medicine part of Diagnostic from Claes N Department, Glostrup, and we are now one big Department Ladefoged et of Clinical Physiology, Nuclear Medicine and PET at both The annual Summer Symposium for the al. Phys. Med. Glostrup and Rigshospitalet, Blegdamsvej. new unified department was celebrated with Biol. 608047 (2015) The prestigious BMJ a relevant tutorial movie and a nice dinner was chosen as the Christmas edition afterwards in Tivoli for all of us. first ever cover image of published our article Physics in Medicine and Biology. The paper “Julestemning i hjernen” describes a clinically viable solution for PET/MR brain attenuation correction.

Postdoc Tina Binderup and Professor Andreas Kjaer participated in a joint project between Icahn School of Medicine at Mount Sinai (NY), Mass. General Hospital & Harvard Medical School (MA), Amsterdam Medical Center and Rigshospitalet that as the first showed Our Head of Department, that FLT-PET can be used as an imaging biomarker The department was the Professor Liselotte Højgaard The department had 3 for cell proliferation in plaques and hematopoietic main organizer of ‘PET/MR received “Chevalier d’lordre de la teams participating activity in atherosclerosis. The results were published brain MRAC workshop II’ at legion d’honnour” from the French in the DHL-race in Circulatory Research. The frontcover illustration was ambassador in Denmark, Kings College London, September made by Postdoc Tina Binderup. Francois Zimeray 2-3, 2015. The workshop was part of a multi-center effort to develop a clinically viable solution for PET/MR brain attenuation correction.

12 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 13 Nuclear Medicine

Diagnostics and treatment Blegdamsvej

Jann Mortensen and Peter Oturai

The KF Section at Blegdamsvej offers a broad va- Diagnostic ultrasound is used as an adjunct to at Rigshospitalet has been accredited as Center procedures are needed to protect the staff in- riety of nuclear medicine and clinical physio- thyroid scintigraphy in patients having thyroid of Excellence by the European Neuroendocrine volved in the direct handling and administra- logical examinations. Among these are PET/CT diseases or hyperparathyroidism. Tumour Society (eNETS). tion. These procedures include whole body for cardiac, neuroendocrine and paediatric dis- counter measurements to ensure no internal eases. Other frequent investigations are SPECT/CT Treatment with 177Lu-DOTATATE to patients 177Lu-DOTATATE - synthesised and labelled at contamination to the staff. and scintigraphy for various pulmological, onco- with neuroendocrine tumors (NET) has been the Hevesy Laboratory at Risø, DTU, and admini- logical, endocrine and nephrourologial diseases. performed in the department since May 2009. stered in our facilities - binds to neuroendocrine For many years the department has successful- Furthermore DXA-scan for bone mineral density Until the end of 2015, 162 patients have been tumors expressing somatostatin receptors. Be- ly treated patients with benign thyroid diseases and whole body composition, lung function test given a total of 561 treatments. We are an active ta-particles from the 177Lu-isotope destroy the – goitre and hyperthyroidism – with 131I-Iodine. and EDTA-clearance for GFR measurement. part of the NET-Center at Rigshospitalet work- tumor cells and the gamma photons are used for ing in close collaboration with the departments scintigraphic imaging and dosimetry. In 2015 we have had weekly and monthly con- To provide these state-of-the-art nuclear medi- of Gastro Surgery, Oncology, Radiology, Pa- ferences dealing with neuroendocrine tumors, cine investigations to most clinical departments thology and Endocrinology at Rigshospitalet. Since May 2014 the department has given 381 thyroid diseases, paediatric oncology, cardiolo- in the hospital the department makes use of: Our performance of more than 550 68Ga-DOTA- Radium-223 treatments to 113 patients with gy, and lung, adrenal and orthodontic diseases. one PET/CT scanner, three hybrid SPECT/CT TOC-PET/CT scans specific for NET diag- castration resistant prostate cancer and symp- cameras, one dual-head gamma camera, four nostics is a central function for the care of tomatic bone metastases. The treatment is single-head cameras, two Jaeger body plethys- the patients at the NET-Center. Patients from given to outpatients from all over the country mographs, and a DXA-scanner. All the equip- Odense University Hospital, Aarhus Univer- as an intravenous injection typically every four ment is extensively used for both routine patients sity Hospital and abroad are referred to us for weeks for a total of six planned series. Since and for research investigations. 177Lu-DOTATATE treatment. The NET-Center 223Ra is an alpha-emitter, extra safety hand-ling

14 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 15 Clinical physiology and nuclear medicine The Glostrup section

Peter Hovind

In 2015 Glostrup Hospital was merged with cameras and two single head gamma cameras. have equipment for measuring blood pressure For testing of lung function, we have a Jaeger A part of our section in Glostrup is a Magnetic Rigshopitalet, and Clinical Physiology and On this equipment we perform many different on the extremities, where blood pressure in the body pletysmograph, where patients with Resonance Imaging (MRI) research group, Nuclear Medicine at the former Glostrup Hos- types of planar and SPECT/CT examinations. lower limbs can be evaluated in patients with COPD, asthma and preoperative lung testing where functional imaging using MRI is per- pital became a part of the Department of Clini- Examples are DAT-scanning, visualising do- claudication or ulcers, as well as equipment are performed. We participate as a part of a large formed in collaboration with the section of cal Physiology, Nuclear Medicine and PET at pamine transport receptor binding in the brain for measurement of systemic blood pressure multicenter study, where a Danish reference Radiology. The research areas are within func- Rigshospitalet. for diagnosing Parkinson’s disease and other over 24 hours for detection and evaluation of material is collected. tional imaging and brain physiology, measure- neurological diseases involving dopamine hypertension in adults and children. We assist ment of perfusion using MRI, cardiac functional The Section of Clinical Physiology and Nu- transport receptors, bone scintigraphy for rheu- in diagnosing secondary hypertension with We have three DXA-scanners, two Lunar Prodigy imaging, normal ageing of the brain as well as clear Medicine residing in Glostrup examines matologic diseases, and evaluation of surgery Captopril renography, Doppler ultrasound of scanners and one Lunar iDXA scanner. The other applications of advanced MRI methods in patients hospitalized at the Glostrup part of performed in the spine with various prosthesis, renal arteries, adrenal vein catherization and two Prodigy scanners are mainly used for the clinical practice and research Rigshospitalet, patients from the outpatient as well as renography for kidney diseases and analysis of urinary steroid metabolism and measurement of bone mineral density in patients clinic the same place as well as patients from follow-up on kidney function in patients with receive patients from the Capital Region and with or suspected for osteoporosis. Our iDXA We have frequent multidisciplinary conferences general practice in the surrounding area. spinal cord injury. Region of Sealand. scanner is at present exclusively used for re- dealing with thyroid diseases, cerebral disor- In the Glostrup section we have a long tradition search purposes where bone mineral density ders, secondary hypertension, geriatric patients of combining classical clinical physiology with We perform classical physiological examination In patients with stroke, we examine the arteries and whole body composition is determined. At and general medical disorders with collaborating modern nuclear medicine methods. with tilt test examination under standardized to the brain for plaques and eventually steno- present we are establishing a Danish reference units and departments at the section. situations with our two Task Force tilt test ses of the vessels. Diagnostic ultrasound is also material consisting of 1,500 healthy controls for For routine nuclear medicine imaging, the sec- monitors, where patients are examined for used together with thyroid scintigraphy in muscle mass in collaboration with the Copen- tion has three dedicated gamma SPECT/CT syncope, episodes of falling and dizziness. We patients with disease in the thyroid. hagen City Heart study.

16 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 17 Radionuclide monitoring of leakage during hyperthermic isolated limb perfusion

Jann Mortensen and Peter Oturai

Since 1993, 5-20 hyperthermic isolated limb Because of the risk of leakage of the cytotox- In 85 % of the patients ≥ 50 % tumor regression perfusions (HILP) have been performed annu- ic drugs (melphalan and TNF-alfa) from the was observed. While no patients had systemic ally at Rigshospitalet as the only center in Den- isolated limb into the systemic circulation, toxicity requiring treatment, considerable or mark. It demands a highly specialized team possibly causing systemic toxicity, leakage is serious local toxicity was observed in 14 %. effort from specially trained plastic surgeons, monitored by a radionuclide technique and anaesthesiologists, perfusionists and nuclear should not exceed a generally recommended medicine specialists. limit of 10 %. Paulsen IF, Chakera AH, Schmidt G, Drejøe J, Klyver H, The indication for the treatment is inoperable Radionuclide monitoring is performed with Oturai PS, Hesse B, Drzewiecki K, Mortensen J. Radio- disseminated melanoma or soft tissue sarcoma continuous, precordial count rate determi- nuclide leakage monitoring during hyperthermic isolated in a limb. nation of in vitro 99mTc-labelled autologous limb perfusion for treatment of local melanoma metastasis erythrocytes infused into the isolated limb cir- in an extremity. Clin Physiol Funct Imaging. 2014 Jun 5. The procedure includes isolation of the circulation. doi: 10.1111/cpf.12164. culation of an extremity by a tourniquet, can- nulation of the artery and vein supplying the Recently we published our results from the Paulsen IF, Chakera AH, Drejøe JB, Klyver H, Dahlstrøm extremity, and connection to a heart-lung ma- procedures performed in melanoma patients K, Mortensen J, Oturai PS, Hesse B, Schmidt G, Drze- chine. This enables regional administration of between 1993 and 2011 in 131 consecutive HILP wiecki K. Tumour response after hyperthermic isolated cytotoxic drugs at doses up to 20 times higher procedures (1,2). 89 % HILP procedures were limb perfusion for locally advanced melanoma. Dan Med J. than the systemically tolerable concentration. completed with a median leakage of 2 % (0-9 %). 2014. Jan; 61(1): A4741.

18 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 19 Paediatric Nuclear Medicine

Lise Borgwardt

In 2015 we performed almost 3,000 paediatric the scan. In the waiting area the children have Our multidisciplinary paediatric haematology amount of medical doctors, PhD students and nuclear medicine investigations, thereof 300 the opportunity to watch the animated deco- and oncology conferences are presented as technicians involved in the field and we con- paediatric PET scans, mainly for the large rations, use apps or watch films at the tablets a web-based nuclear medical platform com- duct research protocols in children primarily paediatric clinics at the hospital. It is a special giving when entering the section or play in the bined with videoconference including districts with PET/MRI in order to develop this inter- focus area for our department to perform these toy corner. outside the capital. Our collaborators are very esting area. investigations at the highest level of excellence, pleased with the possibilities and the advantag- Number of children investigations, <18 years, 2011-2015, and at the same time make it a positive expe- In February we launched the 20 specially pro- es in the diagnostic evaluation of the children. The work in the Paediatric Committee, EANM incl. cancelled investigations rience for both the child and its parents. The duced films and audio essays: “20 stories for this year has been very interesting and inspir- department is a member of the EANM Paedi- the children of Rigshospitalet” sponsored by Our Glostrup Section is specialized in detection ing, and we are looking forward to next year’s atric Committee and the Paediatric Imaging the The A.P. Møller and Chastine Mc-Kinney and evaluation of hypertension in children work in the committee. Harmonization SNM/EANM. Møller Foundation for General Purposes, both with equipment for measurement of systemic films for projection on the ceiling and audios blood pressure over 24 hours. And assists in the In our children section we have a children- essays to listen to while walking around look- assessment for secondary hypertension in chil- friendly PET/128 Slice CT, SPECT/CT, an ing at the wall decoration during tracer uptake dren with Doppler ultrasound of renal arteries, EDTA Clearance room and a renography room. period. We are very happy about this generous receiving patients from the Capital Region and PET/MR-scans are performed in the PET Section. donation and this fantastic work by the artist the Region of Zealand. In each scanner room in the children’s section, that make our children have less sedation and high quality projectors are showing films at the feel entertained and secure while visiting our Research in Paediatric Nuclear Medicine and Number of children investigations, <18 years, 2011-2015, ceiling to secure and entertain the child during department. PET is necessary, as we have an increasing excl. cancelled investigations

20 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 21 Cardiac 82Rb-PET/CT

82Rubidium uptake in metastases from neuroendocrine tumors 62-year-old woman with a neuroendocrine tumor in the small bowel and metastases to Th6, the sternum, the left lung, and mediastinal lymph nodes. Top panel 68Ga DOTATOC PET/ CT imaging with uptake in the above-mentioned foci. Middle and bottom panel 82Rb PET/CT imaging with uptake in the heart and extra cardiac foci during adenosine-induced hyperemic stress and during rest. These foci correspond to the foci on the 68Ga-DOTATOC scan. The images of 68Ga and 82Rb rest do not have the same intensity and color scale and cannot be used for a direct absolute comparison.

Philip Hasbak

Rigshospitalet was the first hospital in Scandi- or with coronary artery bypass graft surgery some and time-consuming in the past, our new are at the brink of potential widespread clinical navia and one of the first in Europe to diagnose (CABG) within 5-7 days according to The cardiac tools now make this state-of-the-art use, especially after the presentation of the ischemic heart disease using cardiac 82Rb-PET/CT Danish National Board of Health. Non-invasive technology readily available. Further, we offer ADVANCE-HF trial. The most widely studied as a new type of advanced imaging system. assessment of myocardial function is an impor- CT coronary angiography (CTCA), which is SPECT tracer, 123I-MIBG has consistently shown tant domain of cardiac 82Rb-PET. Traditionally, useful for planning many invasive cardiac pro- a strong, independent ability to risk stratify pa- At Rigshospitalet there is a special need to cardiac PET images have been visually inter- cedures, particularly complex PCI procedures tients with advanced congestive heart failure. provide cardiac PET every day, since a large preted, using uptake as a measure of function. including chronic total occlusions (CTOs) and Recently we have evaluated 123I-MIBG as an proportion of our patients with ischemic heart This approach, however, takes only a fraction bifurcation stenting. estimate of renal sympathetic nervous activity. disease need an acute or sub-acute work-up of the full PET information into account. The that requires quick decision making as to application of tracer kinetic modelling to Cardiac and renal 123I-MIBG scintigraphy Research-wise we have a close and good coop- coronary revascularisation strategy. Patients dynamically measured data is able to extract In 2010 we introduced cardiac 123I-metaiodo- eration with various clinical departments. with unstable angina or non-STEMI should be objective measures of perfusion and/or me- benzylguanidine (123I-MIBG). Radiotracer ana- revascularised with percutaneous coronary in- tabolism, depending on the tracer. While such logs of the sympathetic mediator norepineph- tervention (PCI) within 3 days after admission true cardiac quantification has been trouble- rine have been investigated extensively, and

22 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 23 Jann Mortensen, Peter Hovind and Peter Oturai

The educational activities have expanded fol- Regarding undergraduate education, nuclear The department’s educational activities have lowing the hospital fusion in early 2015. All medicine technologist students and radiogra- been accredited by the the Accreditation of together the Glostrup Section and the facilities pher students receive part of their education Nuclear Medicine Training Centres Committee of at Blegdamsvej comprize seven educational from the department. The department contri- the Section of Nuclear Medicine of the European positions for young physicians training to butes to the activities of the Faculty of Health Union of Medical Specialists (UEMS) and The become specialists in clinical physiology and Sciences at the University of Copenhagen for Danish Health Authorities. nuclear medicine. Other roles in the specialist medical students, human biology students and education of physicians are related to the dedi medicine & technology students in collabora- Consultant Peter Oturai and Consultant Peter cated courses in oncology, cardiology, pulm- tion with DTU in various subjects, e.g. physio- Hovind are responsible for the postgraduate onology and endocrinology and pathophysiol- logy, nuclear medicine and medical technology. education of physicians in the department. ogy as well as more basic courses in method- Associate Professor Jann Mortensen and Pro- ology (Magnetic Ressonance and Kinetics), all Colleagues and students from Denmark and fessor Henrik Larsson are responsible for the held at our department and arranged by our abroad have visited the department for educa- undergraduate education of medical students professors and consultants. Furthermore, we tional and research purposes for periods rang- in the department. contribute to the specialist education of phy- ing from weeks to months. sicians from other specialities such as urology, nephrology, radiology, oncology, haematology, The department delivers training programmes pulmonology and thoracic surgery. A high to staff from other nuclear medicine and radio- number of PhD students are associated with logical departments in Denmark and the Nor- the research activities in the department. dic countries.

24 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 25 Nuclear medicine technologists, radiographers and lab technicians

Tim Mølgaard Lundby, Kate Pedersen, Lis Larsen and Anne Sørensen

Our group of nuclear medicine technologists, meeting of Danish Society of Clinical Physio- knowledge of the tasks in the whole depart- radiographers and lab technicians are compe- logy and Nuclear Medicine with posters and ment. In the period where we had no dedicated tent, professional and characterized by high presentations a Friday and a Saturday in Sep- quality coordinator our Pharmacist for Quality spirit and dedication in spite of the demanding tember, in radiochemistry meetings for nuclear Assurance Anne-Mette Wittekind from Radio- work with high efficiency. Their dedicated ef- medicine technologists/lab technicians and chemistry has helped with the function also for fort ensures that our patients are investigated in European Association of Nuclear Medicine nuclear medicine and secured that the document without waiting lists and within the demands and Society of Nuclear Medicine international system was updated. Thank you to Anne-Mette from the political and health care system. congresses. We also participate in specific Wittekind for the dedicated work and effort. It courses for upgrade of competences in nuclear is highly acknowledged this flexibility from our We secure this by a voluntary scheme with ex- medicine, dedicated CT courses, courses on staff when the sections help each other. tended opening hours for patient investigations, knowledge of radioactivity and isotopes and treatment with radioisotopes and production. In dedicated courses on organ system diseases Over the year we have put resources into con- 2015 the group has been extended with the new held by national societies and associations and figuration of the new Agfa RIS/PACS System, section Clinical Physiology and Nuclear Med- the local University College Metropol. and it is a challenge. One nuclear medicine icine at Glostrup Hospital due to the fusion of technologist from KF and one from the PET Rigshospitalet and Glostrup Hospital. In February 2015 our employee responsible section and together with the staff nuclear for the quality assurance system, Tina Gade medicine technologists they have worked dedi- The nuclear medicine technologists, radiogra- Jensen, who had been with us for the last 5 years, cated with the configuration. From the Glostrup phers and lab technicians participate actively changed to a new position near her home, and Section the ICT nuclear medicine technologist is in national and international meetings, courses due to the fusion between Rigshospitalet and also involved. We look very much forward to a and congresses. This secures training and life- Glostrup Hospital we postponed the hiering a new RIS/PACS system in 2016 long learning for all through new knowledge new person for the job. This autumn Nuclear and exchange of practical experiences with Medicine Technologist Mette Frederiksen was Radiochemistry Section colleagues from Denmark and abroad. We par- employed as quality coordinator after a job ad- Our five nuclear medicine technologists/lab ticipate in the biannual meetings of the Danish vertisement with very many qualified applicants. technicians start every morning at 6 AM to Society of Clinical Physiology and the Nuclear Mette Frederiksen came from a position as nuclear initiate the production of PET tracers with Medicine and Danish Society of Radiology with medicine technologist in the Nuclear Medicine 18F-FDG for PET. We produce to our own de- oral presentations and posters, in the annual section KF, Blegdamsvej and has a thorough partment and to other hospitals in the greater

26 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 27 Copenhagen region. This year we have initiated The 15 nuclear medicine technologists and 4 We are working on a scheme to optimize the the use of GE Fastlab Synthesis equipment radiographers in the PET scanner section volun- patient throughput and this year we have for the FDG production which means higher teer for extended hours once or twice a week initiated “one day protocol” for parathyroid yields from each production. On Saturdays we to keep the waiting list down. Thank you very scintigraphies instead of the old protocol on produce 18F-FDG for in house use for research much to the staff for this flexibility and helpful two separate days. To secure information and studies on the PET/MRI scanner. attitude. Apart from the daily production all communication Staff Technologist Tim Lundby the nuclear medicine technologists and radio- has implemented an internal messenger sys- Tina Wikke has participated in the develop- graphers participate voluntary in research out- tem that also works on the Glostrup Section, ment of 18F-SFB, which is a key intermediate side opening hours. Some research scans run where Nuclear Medicine Technologist Anne- in the labelling of 18F-ASIS. 18F-ASIS binds to until 10 PM, and sometimes the PET/MRI is grethe Jørgensen has introduced it. tissue factor. Tissue factor is overexpressed in demanding that we start at 6.30 AM. On several cancer types and therefore interesting. Saturday for the special PET/MRI scanner To asure the daily production staff members start Sonja Pedersen Lærke participated in the first study on atherosclerosis in a special animal at 7 AM to secure that the scanners are ready for experiments for production of 68Ga-PSMA for model together with Novo Nordisk we are in the patients at 8 AM. Apart from the daily pro- the diagnosis of prostate cancer. from 6.30 AM to 11 PM. Thank you very much duction all nuclear medicine technologists and ra- to all for this great voluntary and interdiscipli- diograpers participate in research on a volunteer PET scanner section nary research effort. basis outside opening hours. In spring 2015 Nu- In spring 2015 we had a follow up on our clear Medicine Technologist Joo Lærke Yerst had LEAN project and the improvements made Nuclear Medicine Section KF leave to participate in the team in Sierra Leone to in 2013 and introduced new improvements. In 2015 we have renovated our room for patient fight ebola. After Joo Lærke Yerst came home she Instead of making sodiumchloride syringes injections and it is “a walk in lab”, where the gave a talk to the department and to the Danish ourselves, we tested a prefabricated product nuclear medicine technologist can walk in Society of Clinical Physiology and Nuclear Med- from an external provider, and as it was a directly and prepare injections of tracers in- icine about her experiences in Sierra Leone. We cost effective solution, it has been introduced. stead of having to change to go into the clean all pay due respect to Joo Lærke Yerst for the We went through the scheme for patient room. This is another of our LEAN actions, great humanitarian action she participated in. injections of PET tracers and adjusted the and the laborious procedure with clean room scheme to obtain a more efficient program. admittances has been reduced with 25 %. The Mia Hjorth Albers and Joo Lærke Yerst gave a The Glostrup Section has implemented a ments of body composition and bone density Education Booking of PET studies is a complex task, as section has had a rather high exchange of staff course for DSKFNM on the 10th of June on nu- new electronic booking system, Carestream measurements including investigating for In all the clinical sections, PET, KF and the scanners are more than fully booked, and in the nuclear medicine technologist/radiogra- clear medicine and bone pathophysiology and RIS, and a dedicated effort from everyone, muscular strength in hands, legs and exercise Glostrup we have nuclear medicine technolo- as the patient investigations have to be per- pher group, (21 nuclear medicine technologists investigations. including ICT responsible Nuclear Medicine test. gist students, and we are rated positively from formed without waiting lists, and at the same and 4 radiographers). This has been a challenge Technologist Annegrethe Jørgensen, is highly the students and the staff looks upon this task time we need the secure space for research and the organisation and education has been Glostrup Section appreciated. Through the RIS the clinical de- The Glostrup Section held a course about the as a positive asset. They even volunteer for projects. In the department we publish about demanding for everyone, to assure that all The Glostrup Section has both clinical physi- partments and GPs refer patients electronical- brain through DBIO with Staff Nuclear Medi- the young ones to learn how to make blood 150 peer review publications per year. We investigations and all rooms were staffed. We ology examinations and a program of nuclear ly and receive patient reports electronically. cine Technologist Lis Larsen in charge. In the samples. have initiated a new interdisciplinary book- have initiated “a work planner group” with the medicine. The clinical physiology examinations FIU, Functional Imaging Unit, Nuclear Med- ing group with nuclear medicine physicians, staff nuclear medicine technologist and the nu- new to the department are: In 2015 the nuclear medicine technologists icine Technologist Helle Simonsen performs On Blegdamsvej, Mia Hjorth Albers and in medical secretaries and nuclear medicine clear medicine tutors, the clinical teachers and have initiated daily meetings at the black- research and MRI scans. She also teaches in- Glostrup, Annette Foldager are our nuclear technologists. An optimal booking is essen- the nuclear medicine chief technologist. It has p 24 hour blood pressure measurements, in- board. Every day at 8.05 AM the 12 nuclear ternal and external staff members on MRI se- medicine technologist tutors, and they are both tial and demanding, and we have now pro- been a challenge - but now it works well with a cluding in small children, where the section medicine technologists meet at the office of curity, and PhD working at the scanner have responsible for the student education for nuclear longed the task force, and they work together dialogue based planning of the daily schedules has special experience the staff nuclear medicine technologist and to pass a small written examination held by medicine technolgists and radiographers. Nucle- every afternoon. This LEAN follow up effort 3-4 weeks ahead. Meetings at the blackboard p Blood pressure in arms, legs and toes go through the program of the day. The staff Helle Simonsen. She was also in charge and ar medicine technologists Camilla Mose, KF and resulted in a session at the annual meeting in were introduced in 2015 and works well with p Tilt-examinations participates in a big research project on public chair of a two day international course on Elin Lindell, PET are new clinical teachers. Elin European Association of Nuclear Medicine, staff meetings every morning at 8.05. p Ultrasound of carotid arteries health with participation of 1,500 patients Glostrup, DSMMR and ISMRM Nordic Chap- Lindell has passed the Metropol University Hamburg, 2015. p Ultrasound of renal arteries investigated with DXA whole body measure- ter Joint Meeting. College examination as clinical teacher.

28 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 29 PET and PET hybrid systems

Søren Holm

In 2015, the only new, large piece of equip- Tomograph) in close collaboration are performed as full diagnostic quality CT in- to become operational in early 2012. Previous of attenuation correction and artefact suppres- ment in the department was not a PET, but a with the Neurobiology Research Unit cluding contrast enhancement. One of the mCTs attempts to combine the two modalities have sion in order to support the clinical research small animal SPECT/CT (nanoScan) installed (NRU), but the system also works as a is run in a unique well-functioning collaboration either been limited in use (brain “insert” only) protocols. In particular for quantitative results in the Cluster for Molecular Imaging at clinical instrument. with the Department of Radiotherapy, and it is or not fully integrated (two separate gantries). in brain scanning, the lack of direct attenuation Panum, the Faculty of Health Sciences, Uni- extensively used for therapy planning, for which In the mMR, a new amplifier principle in the measurements is a challenge, and we have versity of Copenhagen. Here we also operate The four PET/CT’s in the PET Section are all purpose its large opening (78 cm) is an import- PET detectors makes them insensitive to the been addressing these issues with a post-doc 3 research scanners for PET and CT of small Siemens systems. Two are Biograph TrueV, one ant design improvement over the previous gen- magnetic field, and small enough to allow the and a PhD project in collaboration with Siemens animals. The “older” systems (from 2006) are with 40 and one with 64 slice CT, acquired in eration of systems. PET scanner’s detector ring to be placed inside (Erlangen and Knoxville), University of Leu- a separate PET (Focus 120) and CT (microCAT 2007 and 2009. The other two (from 2010 and the 3-tesla MR-magnet between the gradient ven, and the institute of Computer Science at II). More recently, an integrated PET/CT system, 2011) are mCTs with 64 slice CT and time-of- The most recent (fifth) PET/CT is similar to coils and the RF transmitter. The receiver coils Copenhagen University. the Inveon, was acquired and a Bruker 7T MR flight but overall with rather similar specifica- the two previous mCTs, but with 128 CT-slices. have been redesigned to minimize absorption scanner for small animals was installed. tions, which provides an important flexibility It is installed in the KF Section. This scanner of the PET photons. This makes it possible to Recently the PET/MR installation was comple- in patient scheduling. The majority of the mainly performs paediatric PET scans and perform truly simultaneous measurements of mented with an MR hyperpolarizer (GE SPIN- In the hospital itself, the department has one studies in the PET Section continues to be FDG scans with 82-Rb (heart perfusion), 68Ga-Dota- PET or MR. The combined scanner improves lab), allowing the production of 13C-labelled dedicated, stand-alone brain PET system, five whole-body scans for cancer diagnosis, staging, toc (neuroendocrine tumors), and 18F- NaF, re- the diagnostic power (in particular soft tissue pyruvate, although not yet for human use. combined whole-body PET/CT systems and planning and follow-up, but in the recent years placing some bone scintigraphy or SPECT/CT. differentiation) but also has the potential of one integrated PET/MR system. a significant number of FET, FLT, 11C-PiB, and reducing radiation exposure, which is particu- 68Ga-Dotatoc examinations have been added. All The fully integrated PET/MR scanner (Sie- larly important in children’s examination. The In the hospital brain research continues on the these scans are routinely performed with the use mens mMR) was among the first in the world physics group has been working on the issues PET-only HRRT (High Resolution Research of combined PET and CT, and most CT scans

30 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 31 Cyclotron unit

Holger J. Jensen

During the last years we have experienced a system can serve two 18F targets at the same replacement of the I/O boards (for the more electronics in the RF system (RLC, RPM, stable number of productions at our two cyclo- time. The control system was integrated in than 1,000 digital and analog signals) that is RDRC and RDRA). The original system trons of approximately 1,200±100 per year, see our new S7 PLC cyclotron SCADA system planned to be done early 2016. This part has is more than 22 years old and it is getting figure 1. In 2015 we had in total 1,129 success- in 2014 and 2015, and makes the old IBA been postponed until the RF upgrade was more and more difficult to find spare parts Figure 1 Development in total number of ful productions (512 and 617 for our Scanditro- system obsolete. The new system gives us completely finished. The update gives us a for this subsystem. Consequently a new productions, 18F and 11C productions since nix MC32 and Siemens RDS Eclipse cyclotrons full control and flexibility on all details of modern software- and hardware platform and project were started in 2012, where we 2006. respectively). Last year we had to cancel 6 pro- the system. Hardware, coding and operation an up to date system with modern features of together with Axcon Aps carried out a ductions in total – 4 due to technical difficulties details can easily be copied to other targets easy handling of alarms and coding of new detailed pre-investigation of the system in and 2 due to our RF electronics upgrade project that are planned to be renovated/upgraded logic, the possibility of logging parameters order to establish the necessary knowledge – resulting in a success rate of 98.9 %. As in the in near future (13N, 15O and Rb/Kr). and making various reports and graphs. The to design new electronic boards and to previous years we also managed to keep the p A new target for our Rb/Kr production was upgrade plays an important part in our future estimate the cost for a total replacement. average radiation dose to the employees in the designed and built last year. The target is plans for the MC32 cyclotron. In the new design 46 electronic boards are cyclotron- and radiochemistry unit at a low lev- going to be a replacement for the 23 years replaced with only 8 boards and all parts el, see figure 2. old target. Installation and validation will be are replaced with modern and up to date done primo 2016. technology. The project was funded in 2013, Several upgrade projects are going on for our p A replacement of the original Siemens Simatic build in 2014 and the new modules were Scanditronix MC32 cyclotron: S5 and CP521 based control system from installed January 2015. Except for a few p A new 18F target loading- and unloading 1992 with a new S7 and IGSS based SCADA minor problems the new modules have Figure 2 Average received doses for employees system has been designed and build together system was started in 2012. Most of the p The last project to be mentioned here is been running satisfactory ever since. in the Cyclotron- and Radiochemistry Unit with our colleagues in Uppsala. The target project was finished in 2015 except for the the project on replacing major parts of the since 2006.

32 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 33 Figure 3 The new Rb/Kr target.

The building of the new “Nordfløj” at Rigshos- Centralkomplekset. In 2012 the plans were ac- pitalet has initiated another big project for our cepted by SIS. The funding was finally approved department. Already in 2010 it was realized that in early 2014 and the building project was trans- our existing chimney for release of radioactive ferred to Byg og Teknik medio 2014. gases produced in our growing radiopharmacy production, would not be sufficient to fulfill the The project has been extended, so we as a part of requirement from the authorities (SIS) during this project also extend the target bunker room and after the building of the new building. The for cyclotron 1 and build a new underground requirements are that, we by a risk analysis can bunker for the active charcoal filters. The filter guarantee that no one in the general publication room will be placed at the south-east corner of will receive more than 100 µSv/y from our ac- UK556 and UK566. The filters will be used for a tivities (or approximately 30 times lower than filtration/trapping of radioactive ventilation air the average background dose in Denmark). In from the cyclotrons and the chemistry laborato- 2011 we made a new risk analysis together with ries. All projects are planned to start May 2016. the Wind Energy Section at Risø for a new chimney 2 meter higher than the highest building at Rigshospitalet (as it is demanded in the legisla- tion) and placed at the south-east corner of

34 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 35 70 Radiochemistry 60 50

40 FDG tracer -‐ 30

% non 20

0 2010 2011 2012 2013 2014 2015 Year

The dominance of [18F]FDG is gradually decreasing due to the implementation of new PET radiopharmaceuticals in the department. The percentage of non-[18F]FDG productions over the last six years is shown.

Jacob Madsen and Nic Gillings

Highlights DOTATOC and [11C]PIB was at a similar level but gradually new more specific tracers are preclinical investigations, for example [18F]Apo- p In 2015 we produced the in-house de- compared to 2014. After considerable valida- being introduced for clinical use. In 2015, more Pep-1 for imaging of apoptosis or [18F]HX-4 for veloped uPAR imaging tracer, [68Ga]NO- tion efforts and approval by The Danish Medi- than sixty percent of PET radiopharmaceutical hypoxia imaging. TA-AE105, which was evaluated in a clini- cines Agency, [18F]FDG production on our new productions for humans were non-[18F]FDG cal trial of 10 cancer patients. GE FASTlab modules commenced in August. (see figure above). Neurobiology p In 2015 Valdemar Lykke Andersen and The new system gives higher radiochemical Our collaboration with the Neurobiology Christina Schjøth-Eskesen successfully yields thus providing adequate amounts of [18F] Research Unit, Rigshospitalet and the De- defended their PhD theses in radiopharma- FDG to meet demand from one daily synthesis, Radiopharmaceutical development partment of Drug Design and Pharmacolo- ceutical chemistry. freeing up personnel for other tasks. The new gy, Faculty of Health and Medical Sciences, p In 2015 we took part in a successful ap- system should also be more reliable and use Oncology University of Copenhagen continued in as in plication for an EU grant (Horizon 2020) of the old modules will be phased out within We have started to investigate preparation of previous years. Development and evaluation concerning the development of in vivo click 6 months. Following evaluation of the promis- the prostate imaging agent, [68Ga]PSMA. Vali- of new PET tracers for a number of targets PET imaging agents. Six million Euros was ing uPAR imaging agent, [64Cu]DOTA-AE105 dation and application for human use of this was undertaken in 2015. Among these are [11C] granted to 5 European research groups and in 2014, a gallium-68 labelled version, [68Ga] tracer will take place in 2016. For angiogenesis Martinostat for HDAC and [18F]ASEM for the 68 1 industrial partner for a 5 year period. NOTA-AE105, was evaluated in 10 patients imaging, [ Ga]NODAGA-cRGDyK2 has shown alpha-7 receptor. There were 68 radiophar- p In 2015 a new radiopharmaceutical education in 2015. Production of neuroreceptor tracers promise in animal studies and process opti- maceutical productions for animal studies in program was planned. The first master stu- for various research projects conducted by the mization and validation for human use was 2015. Further evaluation of our in-house de- dents will attend lectures in spring 2016. Neurobiology Research Unit continued on a started in 2015. The first studies in humans are veloped 5-HT2A agonist tracer, [11C]Cimbi-36 par with previous years. planned for 2016. The production of [18F]ASIS continued in 2015. A study investigating the (active site-inhibited factor VIIa) for human use impact of the radiolabelling position revealed Production for clinical and research PET The number of productions of radiopharma- is currently being validated and a clinical trial deeper insight to the metabolic fate of this investigations in humans ceuticals for human use continues to increase, application will be submitted in mid 2016. compound. Furthermore, a [11C]Cimbi-36 do- Production of [18F]FDG and krypton-81m gen- with a total of 1,038 in 2015. In the past, [18F] Several other tracers targeting biological simetry study will commence in 2016. erators along with [18F]FET, [18F]FLT, [68Ga] FDG accounted for the majority of productions processes related to cancer are available for

36 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 37 Radiopharmaceutical Batches Produced Usage/Target [18F]FDG 333 Oncology/Glucose metabolism [68Ga]DOTATOC 266 Neuroendocrine tumors/Somatostatin receptors Krypton-81m generator 146 Lung ventilation [11C]PIB 89 Alzheimer’s Disease/β-amyloid plaques [18F]FET 71 Oncology/amino acid transport [18F]FLT 28 Oncology/cell proliferation tracer [68Ga]NOTA-AE105 10 Oncology/uPAR imaging [15O]Water 7 Cerebral blood flow 11 [ C]AZ10419369 38 Brain Research/5-HT1B receptors 11 [ C]SB207145 34 Brain Research/5-HT4 receptors 11 [ C]Cimbi-36 16 Brain Research/5-HT2A receptors

Radiopharmaceuticals produced for human use in 2015.

Radiopharmaceutical research and PhD projects The promising results obtained with [11C] In January 2015, radiochemist Valdemar Lykke Cimbi-36 encouraged us to look for a flu- Andersen successfully defended his Ph.D. Technetium-99m labelled aprotinin is used orine-18 labelled analogue. In her PhD thesis entitled Development of PET-tracers for routinely for diagnostic scanning of amyloi- project, Ida Nymann Petersen has labelled a the 5-HT7 receptor and in March, Radiochemist dosis patients. In 2014 we developed fluo- number of analogues using various labelling Christina Schjøth-Eskesen successfully defended rine-18 and gallium-68 labelled analogues strategies. Animal testing of these com- her PhD thesis entitled Aziridine Ring-Opening and evaluation of these in an animal model pounds has given mixed results and as yet a Reactions with [18F]fluoride, Strategies in the Syn- of amyloidosis commenced in 2015 and will successful fluorine-18 substitute for 11[ C]Cim- thesis of [18F]-Labelled Peptides and [64Cu]-labelled continue in 2016. bi-36 eludes us. Trastuzumab for Targeting Cancer.

The successful, but rather lengthy, fluorine-18 In vivo click radiochemistry is a promising labelling of ASIS prompted us to search for emerging field in radiopharmaceutical science. faster and more selective labelling strategies. Possibly, it will allow imaging of long-circulat- In his PhD project Troels Elmer Jeppesen has ing nanostructures with short-lived isotopes. In modified the protein (ASIS) and developed flu- 2016, Johanna Steen started her PhD project in orine-18 labelled aldehydes for selective oxime this field. She is evaluating in-house developed couplings as well as copper-64 labelled NOTA carbon-11 in vivo click agents and will develop chelators for copper-free click reactions. fluorine-18 labelled derivatives.

38 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 39 A) Cervix cancer with peritoneal carcinosis and bone metastases easily PET/CT in oncology, depicted on PET/CT. These metastases can be difficult to detect on CT alone. infection and inflammation B) High FDG uptake in all the large vessels indicating vasculitis in a 77 year old man with fever and weight loss.

Annika Loft Jakobsen and Anne Kiil Berthelsen

A B

In oncology indications for PET/CT are diag- the fused images. This provides the clinician Approximately, 50 % of our patients participate clinical results are promising but not yet con- nosis, staging, therapy planning and monitor- with a more precise PET result, a better CT re- in various clinical research protocols. Our main firmed in large randomized protocols. ing, besides detection of recurrent disease in sult, and also a more useful conclusion. To im- topics are gynaecological cancers, malignant patients with a variety of malignant diagnoses. prove the diagnostic quality we have included lymphoma, neuroendocrine tumors, head & Working with PET/CT is fascinating due to the PET/CT is a well-integrated tool due to the a supplementary CT of the lungs with breath neck cancer and lung cancer. great clinical impact of the method as well as the high sensitivity and specificity and has in many hold technique. inspiring collaboration with the clinical depart- workflows replaced other imaging modalities. FDG is still the main tracer in oncology, but we ments and there is no doubt that PET/CT We participate in 17 weekly multidisciplinary also use 18F-NaF, 18F-FET, 18F-FLT, 68Ga-DOTATOC has found its place in the everyday clinical At Rigshospitalet the CT scans of our PET/CT’s team conferences (MDT’s), where our PET/CT and 64Cu-DOTATATE in clinical studies as well work. However, research and clinical trials are are performed as high quality diagnostic scans scan results are discussed with the clinical ex- as in research protocols. still necessary to verify the usefulness of the with the use of oral and intravenous contrast perts. This teamwork is inspiring and crucial for The use of PET/CT in infectious and inflam- method, to refine the scanning protocols as well media. The PET- and the CT scans are inter- improving the diagnostic quality of our PET/CT matory diseases is increasing for diagnostic as to exploit new indications. preted by an expert in nuclear medicine and scan interpretation. The number of PET/CT scans purposes as well as treatment monitoring. The an expert in radiology side-by-side reporting a is still increasing. We also review an increasing idea of exchanging leucocyte scintigraphy with final, combined conclusion taking both the PET number of PET/CT scans performed at other hos- PET is quite obvious for the patient due to the and the CT examinations into account besides pitals, when patients are referred for an MDT. time-saving procedure of the PET/CT, and the

40 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 41 A B A: Standard PET/CT with free shallow breathing of a patient with malignant lymphoma involving the PET/CT- scanning in mediastinum. The image below shows the radiation dose plan based on the PET/CT. radiation therapy B: Breathhold PET/CT of the same patient as in A. Notice the changes in configuration of the tumor volume and the heart due to inflation of the lungs hereby reducing the radiation dose to the heart and lungs.

Annika Loft Jakobsen and Anne Kiil Berthelsen

We now perform 600 PET/CT scans every year The advantages of implementing PET/CT in radiologist hereby optimizing the quality of Research in this field is crucial. We have infor radiotherapy planning of cancer patients the workflow are numerous: the anatomical the method by including all relevant experts creased our focus on breath hold PET/CT not and it has become a daily routine procedure in localisation and the metabolic activity of in the process. We rely on visual analysis only on mediastinal lymphoma which now is our department for patients with brain, head & the tumor are defined, especially when the more than fixed threshold levels due to implemented as a routine procedure hereby neck-, lung-, oesophageal-, cardia-, cervix- and tumor density in CT images is difficult to heterogeneity of most of the tumors. reducing the radiation dose to the heart and vulva cancer as well as malignant lymphoma differentiate from that of the surrounding lungs. Due to this important impact it was and sarcoma. normal tissue. The tissue heterogeneity can In order to utilize the high sensitivity of obvious to focus on the possibility of imple- then be taken into account when choosing PET/CT, our therapy scans are always menting breath hold PET/CT on children. We are fortunate to have an excellent collabo- radiation technique and energy, and only one performed as whole-body examinations Other new indications for this method are be- ration with the Department of Oncology, The scan is necessary. All our PET/CT scanners which in almost one fifth of the cases reveal ing validated in research protocols with lung Radiotherapy Section between all involved have the possibility of performing PET/CT unknown distant metastases or new primary cancer. We are involved in numerous research professional groups. The workflow is facilitat- scans for Radiotherapy planning. The nuclear tumors. These are findings that can change the protocols, local as well as multicentre including ed due to our location in the same building as medicine specialist delineates the viable treatment plan for the patient. the clinical impact of using PET/MR for radio- well as the fact that some of our radiologists are tumors depicted by PET on the fused PET/CT therapy planning. employed in both departments. images after interpretation together with the

42 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 43 Multiparametric PET/MR scans of 8 year old girl with a primary brain tumor (Ependymoma Clinical PET scanning III) showing standard structural MRI (Top) and function tumor characteristics (Bottom) of aminoacid uptake (FET), permeability (CBKi), of the brain blood volume (CBV), and tissue perfusion (CBF). Data collected by Dr L. Marner.

Ian Law and Otto M Henriksen

The Siemens hybrid PET/MR scanner has Our non-FDG radiotracers have had a rela- search tomograph (HRRT) PET scanner, as the been implemented into clinical routine inves- tive increase in the overall production. They growth pattern of meningioma, and the small tigations for dementia. A diagnostic package consist of the amino acid analogue [F18] margins of the stereotactic radiation therapy consisting of 4-5 standard MR sequences fo- Flouro-Ethyl-Tyrosine (FET), the somatosta- used make a 2 mm resolution desirable. cused at localizing cerebral ischemia, infarcts, tin II receptor ligand [Ga68]-DOTATOC, and haemorrhages, tumors and normal pressure [C11]-PiB. [C11]-PiB amyloid binds to amyloid plaques, a hydrocephalus have been combined with pri- pathological hallmark for Alzheimers disease, marily FDG in a short and very comprehensive FET has an established role in the management and is used to support the diagnosis. one-stop imaging shop for dementia. of brain tumor, and is increasingly been evaluated using PET/MR. We are in the process of In 2015 we participated in 1 randomized Our experience is that PET/MR can solve real developing FET PET/MR as a multiparametric clinical treatment trials for Alzheimers disease life clinical diagnostic dilemmas and PET/MR tool in paediatric neurooncology to reduce the in collaboration with the Memory Disorders is indeed a technique that can be used robustly stress of anaesthesia and improve patient man- Research Group. These trials are given a high in clinical practice. In a single 15 min. session agement in this sensitive population. priority as they give access to a potential a patient may receive a thorough and compre- treatment for a serious progressive condition. hensive structural and function neuroimaging For radiotherapy planning and the evaluation Further they enable us to evaluate new tracer examination of outstanding image quality with of recurrent meningioma we are employing technology before they introduced nationally, little risk. [Ga68]-DOTATOC using our high resolution re- e.g. alternative brain amyloid tracers.

44 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 45 PET/MR

Figure 1. Illustrates the number of PET/MR examinations per year.

Johan Löfgren and Adam Espe Hansen

The PET/MR scanner has, since it was in- of radiation exposure compared to traditional roswis, neurobiology and the new multi-modal- Figure 2. PET/MR examination of a left sided hip stalled, mainly been used in clinical, transla- PET/CT where CT normally accounts for 2/3 ity functional molecular imaging based on the prosthesis with complications in a 66 year old male. tional and basic research. The last two years it of the total radiation dose. We are examining combination of PET and hyperpolarized MRI Images illustrate an improved PET image quality after has grown to be a valuable tool especially in the role of clinical PET/MR for a number of (see sections about Research and HyperPET). post processing attenuation correction reconstruction using semiautomatic µmap correction. Coronal PET/MR clinical neurology and neurooncology. In ad- oncologic indications, including treatment We have at the end of 2015, 25 active research images, top row from left (A-C), anatomic MRI (T1 TSE), dition to being a convenient one stop shop for evaluation of lung cancer and cardia cancer, protocols. PET/MR fused and PET with huge attenuation correction the patients it has also facilitated our coopera- as well as radiation therapy planning of can- artifact (white and hollow arrow) due to hip prosthesis. tion with neuroradiology. The number of cers of the head/neck and spine metastases, Bottom row (D-F) show markedly improved PET/MR exams performed has increased steadily over but also for indications as infection. Infection images after semiautomatic µmap correction (black arrow). the years, (figure 1), with the number of clin- is illustrated in Figure 2 showing a PET/MR ical scans in particular dementia (see Section examination of a left sided hip prosthesis with Figure 3. Two PET/MR examinations of a 56 year old male on PET scanning of the brain). complications in a 66 year old male a patient acquired 6 weeks apart, in a gastro oesophageal junction and Figure 3 showing an example of an cancer response evaluation project. Coronal PET/MR images, top row from left (A-C), anatomic MRI (T2 HASTE), I addition to neurology and neurooncology oncology protocol, where PET/MR in this case PET and PET/MR show a gastro oesophageal junction we have over the years gained sufficient expe- is used in a gastro oesophageal junction cancer cancer (black arrows). Bottom row (D-F) show markedly rience and confidence in examining paediatric response evaluation project. shrinkage and reduced metabolic activity of the gastro oncology patients to implement this new and oesophageal junction cancer 6 weeks later (black arrows) promising technique in clinical routine. For Current research topics including oncology, but also reveals a complication - creation of an 8 cm large children the obvious advantage is reduction inflammation/infection, dementia, atheroscle- subphrenic abscess (hollow arrows).

46 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 47 Figure 1. The Language centre are clearly detected, with the cross pointing to Brocca, from which the BOLD signal Magnetic Resonance Imaging has been obtained during a verb generation test paradigm. The patient has a tumor in the opposite hemisphere. provides clinical physiological Figure 2. The figures show results from a patient with left sided internal carotid stenosis, with multiple thrombo-embolic episodes. Perfusion (CBF) is decreased while the cerebral information blood volume (CBV) is increased in the fronto-parietal region,

but the permeability (Ki) seems relatively normal. The mean transit time (MTT), the minimal transit time (minimal TT) and capillary transit tine heterogeneity (CTH) is prolonged in Henrik Larsson the entire region showing altered perfusion.

Functional Imaging Unit (FIU) at Glostrup for further decision making and the surgeon Figure 3. Delineation of the inner and outer border of the has become part of Department of Clini- with a picture of important brain structures to left ventricle in the diastolic phase. Precise delineation cal Physiology, Nuclear Medicine and PET, be spared during operation. of all cardiac phases give raise to the dynamic red curve Rigshospitalet, after Glostrup Hospital and showing the dynamic volume change of the heart. Rigshospitalet have been united in one large There is a growing clinical interest of quan- Figure 4. A three-chamber view through the heart, also hospital in 2015. FIU is heavily involved in tifying brain perfusion (CBF), brain blood called left ventricular outflow tract image, showing left basic physiological research, but there is an volume (CBV) and subtle increase of the atrium, left ventricle and the initial part of aorta during increasing request for clinical investigations of blood brain barrier (BBB) permeability the systole. Here the signal is both very bright and dark patients where functional information is re- (PS product), in patients with brain due to the turbulent flow through narrow aortic valves. quired, and FIU has the knowledge and want tumor and patients with various neu- After visualization of the stenosis, absolute quantification to comply with these requests. Especially rodegenerative and inflammatory of the stenosis is performed using phase mapping of the children with various kinds of brain diseases, diseases. In patients with small and flow through the valves. such as encephalitis, congenital malformation large vessel disease in the brain, and tumors, often suffering from epilepsy re- interest is on mean transit time sistant to medical treatment, are referred be- and variation of the capillary fore neurosurgical intervention. The aim is to transit times. During the last two localize important functional brain centres for decades we have developed the language, motor centres for hands and feet. so-called Dynamic Contrast En- We use advanced ultrafast Magnetic Reso- hanced T1 weighted perfusion nance Imaging (MRI), sensitive for local neu- MRI (DCE-MRI) allowing us brain tumor patients. The method may provide tion, regional wall motion, myocardial perfu- for MR heart examinations. Reading the infor- ral activity dependent perfusion changes with estimate all relevant parame- important information with regards to tumor sion, vascular reserve capacity (the ability to in- mation is done jointly by a cardiologist and us. a concomitant change in the level of deoxyhe- ters in a one-go set-up using a differentiation, recurrence of tumor versus crease perfusion during a stressful stimulation), Figure 3 shows how we can delineate the inner moglobin, so-called BOLD imaging. The level bolus injection of a MR contrast radiation necrosis and treatment response. Fig- delineate non-viable myocardial tissue based and outer border of the left heart ventricle in of deoxyhemoglobin has a profound influence agent. Although computationally ure 2 shows the result of a DCE-MRI of a pa- on the so-called late enhancement, quantify the short axis orientation. Figure 4 shows an ex- on the MRI signal, allowing us to localize the demanding, the measurement is tient with a left sided internal carotid stenosis. level of stenosis or regurgitation through heart ample of a patient with a severe stenosis of the eloquent cortex structure. An example is seen straightforward and cheap to per- valves, depict areas of myocarditis and system- aorta valves. in figure 1, where both the frontal (Brocca) and form using a 3 Tesla MR scanner. MRI is extremely versatile in cardiac diagnostic ic diseases involving the heart as sacoidosis the parieto-temporal (Wernicke) language cen- We are now in the process of imple- imaging, and can provide quantitative informa- and hemachromatosis. Heart patients are being tre are seen in a patient. This kind of informa- menting this method in various clini- tion about right and left ventricular volumes, referred increasingly, and once a week we have tion provide the clinicians with a fundament cal MR scanning protocols, especially in left ventricular myocardial mass, ejection frac- a dedicated time slot at a 1.5 Tesla MRI scanner

48 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 49 64Cu-DOTA-AE105 PET Academic and other activities

First-in-humans study of a new PET tracer that can visualize invasive cancer Andreas Kjær, Professor, Consultant, udvalg Ukendt Primærtumor (DAHANCA), Egill Rostrup, MSc, MD, DMSc, First-in-humans uPAR-PET of prostate cancer. Red arrows on CT show ERC advanced grantee, is President of the National PET/CT Group, the Danish Society of Consultant, Member of the editorial board the prostate gland and blue arrows on PET the uPAR positive tumor Scandinavian Society of Clinical Physiology Clinical Oncology, the Danish Society of Magnetic of the Journal of Cerebral Blood Flow and (images provided by Morten Persson & Dorthe Skovgaard). and Nuclear Medicine (SSCPNM), member Imaging and Diagnostic Imaging Group under Metabolism, Management board of EU COST of the Oncology Committee of the European Danish Lymphoma Group, ERS European Society Action (BM1103): “Arterial Spin Labelling in Association of Nuclear Medicine (EANM), of Radiology. Dementia”, Steering committee of the Healthy national representative of the European Society Aging Clinical Neuroproject at Glostrup. for Molecular Imaging (ESMI), board member of Anne-Mette N. Wittekind, MSc. Pharm., Deputy the Cancer Research Foundation at University of Qualified Person, is member of Dansk Standard. Helle Hjorth Johannesen, Consultant, is member Copenhagen, previous member of the Scientific of Danish Society of Radiology, President of Danish Committee of the Danish Cancer Society, Editor- Annika Loft Jakobsen, Consultant, is involved in Society of Oncoradiology, member of Danish in-Chief of Diagnostics. Leader of project for a various number of clinical research protocols, Society of Medical Magnetic Resonans Imaging and development of theranostics for aggressive teaching at national and international courses Danish Society for Good Clinical Practice. First-in-humans uPAR-PET of breast cancer. Blue arrows on CT show the cancer and for project of hyperPET, funded by pre- and postgraduate for medical doctors, breast tumor. On PET the tumor is clearly uPAR positive the Innovation Fund Denmark, Coordinator of technologists, radiographers and nurses and is Helle Juhl Simonsen, Research MRT, Biomedical (images provided by Dorthe Skovgaard & Morten Persson). an H2020 project on click-chemistry for PET, and invited speaker at national and international Laboratory Scientist, is board member and Andreas Kjær Partner of the Danish Chinese Center for Proteases meetings and congresses. She is supervisor treasurer in the International Society for Magnetic and Cancer funded by the National Natural for several PhD students and responsible for Resonance in Medicine (ISMRM)/Nordic Chapter, Science Foundation of China and the Danish the specialist course in Oncology for Nuclear Chair of the local organizing committee for Prediction of cancer aggressiveness and meta- develop PET based imaging for non-invasive testing and after approval by the Danish National Research Foundation. National Director Medicine Physicians. She is a member of the DSMMR & ISMRM Nordic Chapter joint meeting, static potential is urgently needed for better visualization of the aggressive cancer pheno- Medicines Agency, a clinical phase I trial in 10 of EATRIS (the European Advanced Translational “European Organisation for Research and MRI from head to toe, April 2015. Member of selection of best therapeutic strategy in the type. As target was chosen the urokinase-type patients with prostate, breast or bladder cancer, Research Infrastructure in Medicine), Head of Treatment of Cancer” (EORTC). Member of the the Membership Committee, the Nominations individual patient, i.e. for tailoring therapy plasminogen activator receptor (uPAR), a all cancer types where FDG-PET is of limited the Cluster for Molecular Imaging and Director Oncology Committee of EANM, and member of Committee, the External Relations Sub-Committee (personalized medicine). As an example, the proteolytic system that has been shown to be value, was undertaken at our department in of the PhD Program for Medical & Molecular BIR, Danish Society of Oncologial Radiology and Global Relations and the Publications Committee treatment strategy for prostate cancer ideal- responsible for invasion of surrounding tissues close collaboration with the clinical depart- Imaging at the Faculty of Health and Medical Danish Society of Clinical Physiology and Nuclear in International Society for Magnetic Resonance in ly depends on aggressiveness of the tumor. by solid tumors such as prostate and breast ments of Breast Surgery, Urology and Oncology Sciences, University of Copenhagen. Co-chair Medicine. Member of Regional Working Groups Medicine (ISMRM)/Section for MR Technologist However, currently there is no efficient way cancer, and thereby predicts metastatic spread. at Rigshospitalet. of the Lundbeck Foundation Clinical Research for implementation of clinical guidelines for: (SMRT), Member of the Members and Services to stratify these tumors. Accordingly, in pros- Basic research in uPAR has been pioneered by Fellowship Program (US-DK). Member of the colorectal liver metastases, lymphoma, malignant Committee, the Structure and Governance tate cancer, where the majority of tumors are the Finsen laboratory in Copenhagen. Results obtained from this first-ever study of Academy of Technical Sciences (ATV). melanoma, cancer of unknown primary, and Committee in European Society for Magnetic non-aggressive, the lack of effective tools leads uPAR-PET in humans, which were recently suspicion of severe disease. Member of National Resonance in Medicine and Biology (ESMEMB). to substantial overtreatment and in those pa- In collaboration with both national and inter- published in the journal Theranostics, were most Anne Kiil Berthelsen, Consultant, is member of Working Groups for Lymphoma (Chair of tients to unnecessary side effects such as erec- national partners, a total of 10 PET tracer can- encouraging: high uptake in tumors and the International Lymphoma Radiation Oncology the Diagnostic Imaging Group under Danish Henrik B. W Larsson, MD, DMSc , Consultant, tile dysfunction. didates have been synthesized, radiolabeled metastases and a low radiation burden to the Group, Steering Committee (ILROG), “European Lymphoma Group (DLG) and pharyngeal/ Head of Functional Imaging Unit, Professor in and tested in human xenograft tumor mouse patient. Accordingly, further studies using Organisation for Research and Treatment of laryngeal cancer). Member of the Steering Group Clinical and Comparative Physiology, Institute To serve this unmet medical need for identi- models over the last years. Based on these pre- uPAR-PET are currently planned. Examples of Cancer Lymphoma Group ” (EORTC), the Danish for Danish Liver and Biliary Cancer and board of Clinical Medicine, The Faculty of Health fication of aggressive cancers, a translational clinical results, a most promising candidate, images obtained by the first-in-humans Society of Radiology, the Danish and the Nordic member of DGCG (Danish Gynecological Cancer and Medical Science, Copenhagen University, research program headed by Professor Andreas 64Cu-DOTA-AE105, was selected for clinical uPAR-PET study are shown below. Society of Gynaecological Oncology, British Group) and DCCG (Danish Colorectal Cancer Denmark, Representing professor (Ordførende Kjær was initiated several years ago in order to translation. Following rigorous toxicological institute of Radiology (BIR), Billeddiagnostisk Group). professor) in Clinical Physiology and Nuclear

50 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 51 Medicine, Institute of Clinical Medicine, Physiology” for Nuclear Medicine physicians Rigshospitalet, Chair of the Pediatric Focus Group Technology Bioengineer programme, member of Authority he is responsible for the theoretical part Søren Holm, Chief Physicist, is member of the The Faculty of Health and Medical Science, and Respiratory Physicians, he is the responsible at the Department of Clinical Physiology, Nuclear the European Association of Nuclear Medicine of the specialist training in Clinical Physiology EANM Physics Committee with special tasks Copenhagen University, Denmark, Professor physician for Nuclear Medicine in the Faroe Medicine and PET and member of the Process (EANM) and the Danish Society of Clinical and Nuclear Medicine in Denmark. He is the in Radiation Protection, a delegate for DSMF to in Medical Magnetic Resonance Imaging, Islands, member of the steering committee Group for the development of the Children’s Physiology and Nuclear Medicine (DSKFNM). Head of the Doctors Clinical Physiology and the European and International organisations Norwegian University of Science and Technology, of “Dansk Lungecancer Gruppe” (Danish Hospital at Rigshospitalet. She is involved in Affiliated to the Centre of Excellence for Nuclear Medicine Training Committee of the for Medical Physics (EFOMP and IOMP), board Norway, Responsible for specialist course in Lung Cancer Group), the subcommittees for clinical research protocols, supervisor for PhD Personalised Medicine of Infectious Complications Danish Society for Clinical Physiology and member of the Nordic Society for Radiation tracer kinetic theory, math and statistic for nuclear “Dansk Diagnostisk Lungecancer Gruppe” students, teaching at national and international in Immune Deficiency (PERSIMUNE) and the Nuclear Medicine and member of the board of the Protection (NSFS), member of one IAEA advisory medicine physicians. Responsible for specialist (Danish Diagnostic Lung Cancer Group) and courses pre- and postgraduate for medical steering committee of MATCH (Managing of Post- Danish Endocrine Society (DES) and the Niels A. group concerned with QA/QC and image course in functional imaging (MRI, PET-MRI, UL) “Lungecancer Screeningsgruppen” (Screening doctors and is invited speaker at national and Transplant Infections in Collaborating Hospitals). Lassen Foundation. He is co-editor for the Danish artefacts affecting SPECT/CT and another IAEA for nuclear medicine physicians, Management of Lung Cancer Group), member of the steering international meetings and congresses. Elected member of the board of representatives, the Medical Journal in the medical imaging section. advisory group regarding staffing in Medical board of EU COST Action (BM1103): “Arterial committee and the quality subcommittee for Association of Consultants in Denmark. He is responsible for the postgraduate education Physics, member of Sundhedsfagligt Råd i Klinisk Spin Labelling in Dementia”, Steering committee creating Danish reference values for lung function Liselotte Højgaard, Professor, Head of in the Glostrup section of the department. Fysiologi og Nuklearmedicin in the Capital of the 7 Tesla project, Copenhagen, Denmark. and member of an editorial board. Department. Chairman of the Board of the Maria Helene Pejtersen, Nuclear Medicine Region, the Specialty Advisory Committee (SFR) Danish National Research Foundation. She is Technologist, is member of the Symposiagroup for Peter Oturai, Consultant, is responsible for the in Clinical Physiology and Nuclear Medicine and Ian Law, Professor, Consultant, is Member of the Kim Francis Andersen, Staff Specialist, is member Member of Conseil d’Administration, INSERM, Technologists at Rigshospitalet. postgraduate education of physicians in the external lecturer at Copenhagen University. Neuroimaging Comittee, European Association of of the Board of Danish Sarcoma Group (DSG). He L’Institut National de la Santé et de la Recherches department. He is Danish delegate, representing Nuclear Medicine (EANM), Member of the “PET teaches at specialist courses for nuclear medicine Médicales, Frankrig. Advisor to the French Marianne Federspiel, Nuclear Medicine Danish Society for Clinical Physiology and Tim Lundby, Staff Technologist, is member of Response Assessment in Neurooncology (RANO) physicians and orthopedic surgeons. Government in the strategic “Médecine du Technologist, is member of EANM Technologists Nuclear Medicine (DSKFNM), in the European Lederrådet i Danske Bioanalytikere. working group” under the European Association Future”. Chair of EU Science Advisory Board in Committee. Union of Medical Specialists (UEMS) and deputy of Nuclear Medicine (EANM), European Linda Kragh, Chief Nuclear Medicine Health Research. She represents the University of delegate in the European Association of Nuclear Ulrik B. Andersen, Consultant, Co-supervisor Association of Neurooncology (EANO), and Technologist, is member of Sundhedsfagligt Råd Copenhagen, Rigshospitalet in the Medicine and Marie Øbro Fosbøl, Senior Registrar, Medicine (EANM). He has been representing for PhD students in the department. Former Society of Neurooncology (SNO). Member of the i Klinisk Fysiologi og Nuklearmedicin i Region Technology Bioengineer program, the Technical President of Society of Young Nuclear Medicine DSKFNM in the Danish Health and Medicines member of the board of Danish Society of Danish Neurooncology group (DNOG). Member H, SFR, (the Speciality Advisory Committee in University of Denmark (DTU), where she is Physicians (YNK), member of the board of Authority’s committee for speciality planning Hypertension. Member of European Society of of the working group for ”Clinical Guidelines Clinicial Physiology and Nuclear Medicine in the also adj. professor. Elected Member of the Royal Danish Society of Clinical Physiology and of Clinical Physiology and Nuclear Medicine Hypertension and acknowledged hypertension for the Treatment of Brain Metastases”, Danish Capital Region), Head of the DRG Committee Danish Academy of Sciences and Letters, member Nuclear Medicine (DSKFNM) and member of (CPNM). He is member of the Danish Thyroid specialist by this society. Responsible for the Neurosurgical Society (DNKS), responsible for the of DSKFNM, member of Uddannelsesforum of ATV “The Danish Academy of Technical the course committee in clinical physiology and Cancer Guideline Group (DATHYRCA), member specialist course in cardiovascular circulation specialist training course in the central nervous for bioanalytikeruddannelsen i Region H, Sciences”, member of the Olav Thon Foundation, nuclear medicine. of the Doctors CPNM Training Committee for nuclear medicine physicians in Denmark. system for nuclear medicine physicians. (the Speciality Council for the Education of Science Advisory Board, member of the Board of and member of the CME and Educational Member of the Danish Society of Clinical Technologists in the Capital Region) and member the Crown Prince Frederik and Crown Princess Otto Mølby Henriksen, Consultant, PhD, is Committee – both affiliated to DSKFNM. He is Physiology and Nuclear medicine, Danish Society Jacob Madsen, Chief Production Manager, is of Uddannelsesudvalget på Radiografuddannelsen Mary’s Foundation and member of the Board of member of the DRG Committee in Danish Society responsible for the specialist course in Endocrine of Cardiology and Danish Society of Diagnostic member of the board of DSKFNM (Danish Society at Metropol (the Speciality Council for the Arvid Nilssons Foundation and Tagea Brandt’s for Clinical Physiology and Nuclear Medicine Pathophysiology for CPNM physicians in Ultrasound. of Clinical Physiology and Nuclear Medicine). Education of Radiographers at Metropol). prize. (DSKFNM). Denmark.

Jann Mortensen, Clinical Associate Professor, Lise Borgwardt, Consultant, is Scientific Malene Fischer, Clinical Professor of Research, Peter Hovind, Consultant, participates in several Robin de Nijs, MSc, PDEng, PhD, Specialist Consultant, is member of “Den Regionale Committee member of the EANM, member at the Consultant, is supervisor for several PhD students clinical research protocols and is co-supervisor Medical Physicist, is member of EANM’s Network Videnskabsetiske Komité F for Hovedstaden Pediatric Committee under EANM, member of the and involved in both pre- and postgraduate for a PhD Student. As the Head of the specialist of Excellence for Brain Imaging, member of the (Regional Ethics Committee). He is responsible Pediatric Imaging Harmonization Group, member teaching. Course Director of “Introduction to courses in Clinical Physiology and Nuclear Danish Society for Medical Physics and lecturer at for the specialist course in “Clinical Respiratory of the Tumorboard for Pediatric Solid Tumors at Clinical Medical Imaging” at the Medicine and Medicine under the Danish Health and Medicines EFOMP’s school for Medical Physics Experts.

52 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 53 Osteodens. dual X-ray absorptiometri (DXA), radius 139 CT pelvis SPECT/CT 77 Osteodensitometri, dual X-ray absorptiometri collum fem. 4,022 CT abdomen SPECT/CT 294 DXA, body composition 827 CT lower extremities SPECT/CT 22 Studies 2015 Total 8,292 CT upper extremities SPECT/CT 2 CT wb PET/CT (KF) 1,212 Endocrine organs CT wb PET/CT (PET) 5,129 Thyroid scintigraphy, 99mTc-Pertechnetat 513 MR wb PET/MR 356 Myocardial perf. scintigr. gated, 99mTc-MIBI, pharmacol. stress, adeno. 1 Blegdamsvej Thyroid scintigraphy, 123I-Iodide 1 CT lover extremities PET/CT 50 Myocardial perf. scintigr. gated, 99mTc-MIBI, NTG 1 Thyroid, ultrasound 513 123 Second opinions external PET, PET/CT, SPECT/CT, CT and MR 1,178 Myocardial I- MIBG, sympaticus activity 27 99m CNS and peripheral nervous system Thyroid scintigraphy, Tc-Pertechnetat, SPECT 1 Extra tumor delineation 105 Myocardial calcium score 558 99m 15 Parathyroid scintigraphy, Tc-Stamisis 10 Regional cerebral blood flow, DIAMOX, O-H O 3 18 Other investigations 218 2 PET myocardial metabolism, F-FDG 50 99m 15 Parathyroid scintigraphy, Tc-Stamisis, SPECT 43 Regional cerebral blood flow, O-H2O 4 82 Supplementary/repeated imaging 2,526 PET myocardial perfusion, Rb 564 123 18 Tumorscintigraphy, I-Iodide 1 Regional cerebral metabolism, F-FDG 834 82 Total 28,189 PET myocardial perfusion, Rb, pharmacological stress, adeno 555 123 11 Tumorscintigraphy, I-Iodide, rh-TSH 30 Regional cerebral receptor, C-PIB 139 CT cardiac angiography 24 123 18 Adrenal marrow scintigraphy, I-MIBG 38 Radiotherapy Regional cerebral receptor, F-FET 393 Total 3,306 177 131 11 Scintigraphy after Lu- Dotatate therapy 145 Treatment with I, benign thyroid 42 Regional cerebral receptor, C different tracers human (NRU) 89 177 11 Total 1,295 Isotope treatment with Lu-Dotatate 124 Regional cerebral receptor, C differenct tracers animal (NRU) 25 223 18 Peripheral vessels Isotope treatment with Ra-Dichlorid 273 Regional cerebral receptor, F-Florbetapir 11 99m 18 Isolated limb perfusion leakage monitoring, Tc-erythrocyt 8 Blood and lymph system Total 439 Regional cerebral receptor, F-FLT 42 Total 8 Erythrocyt volume, 99mTc-erythrocytter 16 Regional cerebral receptor, 68Ga-Dotatoc 34 Plasma volume, 125I-HSA 16 In vitro analysis CT-scanning of cerebrum 323 99m Gastrin intestinal tract, liver, biliary tract and pancreas Lymph scintigraphy, extremities, Tc- Nanocolloid , stasis 1 Plasma and protein analysis 3.792 MR-scanning of cerebrum 413 99m Salivary gland scintigraphy 99mTc-Pertechnetat 19 Lymph scintigraphy, extremities, Tc-HSA, leakage 1 Gene expression analysis 10.994 Total 2,310 99m Biliary tract scintigraphy, 99mTc-Mebrofenin 32 Sentinel node scintigr. tumor drainage, c. mammae, Tc-Nanocolloid 33 Immunohistiochemistry 1.465 99m Meckels diverticulum scintigraphy, 99mTc-Pertechnetat 4 Sentinel node scintigr. tumor drainage, mel. malign., Tc-Nanocolloid 160 Flow cytometry 7.396 Respiratory organs 99m Bleeding scintigraphy (abdomen) 99mTc-erytrocytter 1 Sentinel node scintigr. tumor drainage, c. penis, Tc-Nanocolloid 27 Total 23.647 Lung function test, whole body plethysmography 1,832 99m Total 56 Sentinel node scintigr. tumor drainage, c. vulvae, Tc-Nanocolloid 34 Lung function test, whole body plethysmography w/reversibility 143 Sentinel node scintigr. tumor drainage, head/neck, 99mTc-Nanocolloid 100 Lung function test, spirometry, 1,980 Sentinel node, peroperative with gamma probe, 99mTc-Nanocolloid 2 Kidneys and urinary tract Lung function test, spirometry w/reversibility 100 Peritumoral injection of 99mTc-Nanocolloid for sentinel node 688 Glomerular filtration, 51Cr-EDTA, several samples 93 Glostrup Lung function test, diffusion capacity (CO) 4,002 Spleen scintigraphy, 99mTc-erythrocyte, heated 4 Glomerular filtration, 51Cr-EDTA, one sample 4,046 Lung function test, peak flow w/ reversibility 3 Total 1,082 99m Max. insp. abd exspir. muscle pressure 117 Renal scintigraphy, Tc-DMSA 20 CNS and peripheral nervous system 99m 99m 99m Lung perfusion scintigraphy, Tc-MAA 9 Renography, Tc-MAG , diuresis 45 Other diagnostic procedures Regional cerebral blood flow, Tc- HMPAO, pharm.prov. 22 99m 99m 99m Lung perfusion scintigraphy, regional, Tc-MAA 18 Renography, Tc-MAG 3, graft 3 Aprotinin scintigraphy, 99mTc-Aprotinin 4 Regional cerebral blood flow, Tc- HMPAO 81 99m 99m Lung perfusion scintigraphy, SPECT, Tc-MAA 290 Renography, Tc-MAG 3, ACE-inhibitor 47 PET tumor scanning, 18F-FDG 5,109 Regional Dopamine Transporter (DAT) receptor imaging, 123I-FP-CIT 321 81m 99m Lung ventilation scintigraphy, Kr-gas 14 Renography, Tc-MAG 3 1,898 PET scanning, 18F-FDG 310 MR-scanning of cerebrum 1,606 81m 99m Lung ventilation scintigraphy, regional, Kr-gas 156 Renography, Tc-MAG 3, dual head 9 PET infection scanning, 18F-FDG 101 Total 2,030 81m 123 Lung ventilation scintigraphy, SPECT, Kr-gas 292 Sympaticus activity, kidneys, I-MIBG 48 PET tumor scanning, 68Ga-Dotatoc 613 99m Lung ventilation scintigraphy, SPECT Tc-Technegas 2 Total 6,209 White blood cell scintigraphy, 99mTc-white blood cell 18 Respiratory organs 99m Mucociliary clearance, Tc-Venticolloid 32 White blood cell scintigraphy, 99mTc-white blood cell, SPECT 26 Lung function test, whole body plethysmography 471 18 PET thorax F-FDG PET/CT breathhold 2 Bone and joint White blood cell scintigraphy, 111In-white blood cell 11 Lung function test, spirometry 474 CT thorax PET/CT breathhold 8 Bone scintigraphy, 99mTc-HDP, regional, static 39 White blood cell scintigraphy, 111In-white blood cell, SPECT 7 Lung function test, spirometry w/reversibility 133 Total 9,000 Bone scintigraphy, 99mTc-HDP, whole body, static 598 Whole body, contamination measurement 148 Lung function test, diffusion capacity (CO) 472 Bone scintigraphy, 99mTc-HDP, SPECT 617 Image fusion (PET, SPECT, MRI, CT or planar) 9,351 Max. insp. abd exspir. muscle pressure 4 Heart and cardiovascular system Bone scintigraphy, 18F-fluorid, whole body, static 6 CT head/neck SPECT/CT 224 Lung perfusion scintigraphy, SPECT, 99mTc-MAA 68 Isotope cardiography, RVEF pass, 99mTc-HSA 2 Osteodens. dual X-ray absorptiometri (DXA), columna lumb. 2,041 CT wb SPECT/CT 606 Lung ventilation scintigraphy, SPECT 99mTc-Technegas 65 Isotope cardiography, LVEF, 99mTc-HSA 1,524 Osteodens. dual X-ray absorptiometri (DXA), lat.spine 3 CT thorax SPECT/CT 492 Total 1,687

54 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 55 w

Heart and cardiovascular system DXA, body composition 9 64Cu-DOTATATE 29 Myocardial perf. scintigr. gated, 99mTc-MIBI, pharmacol. stress, adeno. 247 MR scanning hands and fingers 46 68Ga-RGD 22 Myocardial perf. scintigr.99mTc-MIBI 178 MR scanning wrist 68 82Rubidium 22 Tilt table test 297 MR scanning sternum 1 MR-scans 32 Finance Analysis of heart rate variability 199 MR scanning thorax 4 CT-scans for image fusion 22 MR scanning of the heart 104 MR scanning columna thoracalis 59 Rats Total 1,025 MR scanning columna cervicalis 59 18F-FDG 59 MR scanning columna lumbalis 59 82Rubidium 112 Peripheral vasculature MR scanning os sacrum 59 MR-scans 4 Systolic blood pressure, fingers 6 MR scanning pelvis and hips 59 MR-scans, Late Gadolinium Enhancement 108 MR scanning femur 108 MR-scans DWI 4 Systolic blood pressure, ancle and toes 467 Turnover Systolic blood pressure, ancle-brachial index after treadmill 112 Total 10,915 CT-scans for image fusion 137 24 hours blood pressure measurement 344 Optical imaging 7 250 Doppler ultrasound of carotid arteries 4,334 Endocrine organs Radiotherapy 42 240 99m 230 Total 5,263 Thyroid scintigraphy, Tc-Pertechnetat 440 Mices 220 Thyroid, ultrasound 454 13C-PIB 23 200 Thyroid, fine needle aspiration biopsy 33 18F-ASIS 28 Gastrin intestinal tract, liver, biliary tract and pancreas 180 131 18 99m Iodine uptake test, I-Iodide 14 F-FDG 618 160 Salivary gland scintigraphy Tc-Pertechnetat 2 Catheterization, adrenal vein sampling 10 18F-FET 293 140 Doppler ultrasound of splanchnic blood flow 409 Synacthen test 86 18F-FLT 69 120 Glucose tolerance test 16 100 Total 1,037 18F-Aprotinin 27 Lactose tolerance test 20 80 124Iodine 16 Helicobacter pylori testing 52 60 18 Kronepoints" in mio DKK F-HX4 – hypoxi-tracer 16 " 40 Iron uptake test 1 Other diagnostic procedures 99m 64Cu-Albumin 17 20 Total 500 White blood cell scintigraphy, Tc-white blood cell 16 64 0 White blood cell scintigraphy, 99mTc-white blood cell, SPECT 12 Cu-DOTA-AE105 4 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 White blood cell scintigraphy, 99Tc-leucoscan 3 64Cu-TRIS 2 Year Kidneys and urinary tract 64 Assessment of blood samples 3 Cu-liposomes 251 51 Glomerular filtration, Cr-EDTA, several samples 3 64 MR scanning upper abdomen 54 Cu-liposomes, targeted 42 51 The increase in activities measured in ”krone point” rose from 61,6 mio Glomerular filtration, Cr-EDTA, one sample 589 64 MR scanning lower abdomen and pelvis 54 Cu-Na 2 99m DKK in 2005 to 243,5 mio DKK in 2015. Renal scintigraphy, Tc-DMSA 2 64 Total 142 Cu-ASIS 53 99m Renography, Tc-MAG 3 , diuresis 2 64Cu-Aprotinin 27 99m “Krone point”: Price for each patient investigation multiplied with Renography, Tc-MAG 3 524 64Cu-X 16 99m Radiotherapy Renography, Tc-DTPA, ACE-inhibitor 167 68 number of investigations, summarized for all patient studies performed 131 Ga-DOTATOC 25 99m Treatment with I, benign thyroid 14 Renography, Tc-DTPA 80 68 during the year. Total Ga-RGD 36 Doppler ultrasound of renal blood flow 370 18 13 14 F-FDG/ C-Pyruvate 40 Ultrasound kidneys 363 13C-Pyruvate s 10 CT kidneys 463 Animal studies MR-scans 777 Balance 2015 CT bladder 463 MR-scans DWI 55 Total 3,026 Dogs MR-spectroscopy 55 Expenditure (DKK mio.) 18F-FDG 4 Optical imaging 954 Running costs 24.4 18 13 Radiotherapy 240 Bone and joint F-FDG/ C-Pyruvate 12 Staff 70.9 Bone scintigraphy, 99mTc-HDP, regional, static 10 18 13 CT-scans 44 F-Asis/ C-Pyruvate 1 In total 94.3 Bone scintigraphy, 99mTc-HDP, whole body, static 335 64Cu-liposomes 22 CT-scans for image fusion 1,252 99m Total 5,661 Bone scintigraphy, Tc-HDP, SPECT 186 CT–scans for image fusion 23 Osteodens. dual X-ray absorptiometri (DXA), columna lumb. 3,066 MR-scans 4 Receipts 19.7 Osteodens. dual X-ray absorptiometri (DXA), lat.spine 742 Pigs Osteodensitometri, dual X-ray absorptiometri af collum fem. 6,045 18F-FDG 3 Total number of studies 115,133

56 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 57 Equipment 2015

Equipment Product Purchase year Equipment Product Purchase year

Blegdamsvej Cluster for Provivo/ADAC mobile gamma 1990 Molecular Imaging camera PET scanner GE 4096 1991 Gamma cameras Mie-Scintron 2004 SPECT Mediso Nucline X-Ring/R 2004 Mediso N-TH45-D 2008 Siemens Micro-PET Focus 120 2006 DDD SoloMobile 2012 Micro-CT Siemens Micro-CAT II 2006 SPECT cameras Philips ADAC Skylight 2002 Phosphor Imager Perkin Elmer cyclone 2007 Mediso Nucline X-Ring-R/HR 2009 Bruker preclinical MRI PharmaScan 7T 2013 SPECT/CT cameras Philips, Precedence 16-slice CT 2006 Siemens preclinical PET/CT Inveon 2013 Philips, Precedence 16-slice CT 2008 PX Inc. preclinical RT X-RAD 320 2013 Siemens Symbia 16-slice CT 2011 PET scanners HRRT Siemens/CTI 2007 PET/CT scanners Siemens Biograph TrueV 40-slice CT 2007 Siemens Biograph TrueV 64-slice CT 2009 Siemens mCT-S (64) 2010 Glostrup Siemens mCT-S (64) 2011

Siemens mCT-S (128) 2013 Gamma cameras Mediso Nucline TH45 2007 PET/MR scanner Siemens mMR 2011 Mediso Nucline X-Ring 2003 GE SPINlab MR Hyperpolarizer 2014 DDD SoloMobile 2012 Lung function Jaeger Masterscreen w/bodybox 2005 SPECT/CT cameras GE Infinia Hawkeye 2004 Jaeger PFT pro w/bodybox 2007/13 Siemens SymbiaT2 2006 DXA scanner GE Lunar Prodigy 2011 GE Discovery 670 2010 Whole body counter WBC w/Nal counting chamber 1977 DXA scanner GE Lunar iDXA 2014 WBC w/plast counting chamber 1978 GE Lunar Prodigy 2005 Cyclotrons Scanditronix 32 MeV 1991 GE Lunar Prodigy 2004 RDS Eclipse cyclotron, CTI 2005 Lung function Jæger Masterscreen w/bodybox 2007

58 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 59 Aneheim E, Halleröd J, Albertsson P, Jensen H, A, Toft G, Bonde JP, Spanò M, Malm G, Haugen de Nijs R. Critical values for Pearson’s second Holgersson S, Lindegren S. Shelf-life of ε-lysyl-3- TB, Giwercman A. No association between coefficient of skewness. Journal of Statistics (trimethylstannyl)benzamide immunoconjugates, body mass index and sperm DNA integrity. Education. 2015;23(1):1-3. Publications 2015 precursors for 211At labeling of antibodies. Cancer Human reproduction (Oxford, England). 2015 de Nijs R. Comment on: A Poisson resampling Biotherapy & Radiopharmaceuticals. 2015 Jul;30(7):1704-13. method for simulating reduced counts in nuclear Feb;30(1):41-5. Barloese MCJ, Mehlsen J, Brinth L, Lundberg HIS, medicine images. Physics in Medicine and Biology. Aneheim E, Jensen H, Albertsson P, Lindegren S. Jennum PJ, Jensen RH. Reduced Baroreflex 2015 Jul 21;60(14):5711-5. Theses response. Defended on the 15th of September 2015, Primary Tumor Metabolic Activity Using 18F-FDG Astatine-211 labeling: a study towards automatic Sensitivity in Cluster Headache Patients. Debes N, Jeppesen S, Raghava JM, Groth C, Rostrup Andersen VL. PhD thesis. Development of probes University of Copenhagen. PET/CT as a Predictor of Survival in 92 Patients production of astatinated antibodies. Journal Headache. 2015 Jun;55(6):815-24. E, Skov L. Longitudinal Magnetic Resonance for in vivo molecular brain imaging of serotonin Schjoeth-Eskesen C. PhD thesis. Aziridine ring- With High-Grade Bone or Soft Tissue Sarcoma. of Radioanalytical and Nuclear Chemistry. Bashir A, Ziebell M, Fugleholm K, Law I. A Potential Imaging (MRI) Analysis of the Developmental markers. Defended on the 16th of January 2015, opening reactions with [18F]fluoride, strategies Medicine (Baltimore). 2015 Jul;94(28):e1142. 2015;303(1):979-983. Role of 68Ga-DOTATOC PET in Modyfying Changes of Tourette Syndrome Reveal Reduced University of Copenhagen. in the synthesis of [18F]-labelled peptides and Andersen KF, Albrecht-Beste E. Brown Tumors Due Asghar MS, Pereira MP, Werner MU, Mårtensson Eligibility to Surgery in Patients with Recurrent Diffusion in the Cortico-Striato-Thalamo- Brinth LS. PhD thesis. Carotid sinus hypersensitivity [64Cu]-labelled trastuzumab for targeting cancer. to Primary Hyperparathyroidism in a Patient J, Larsson HBW, Dahl JB. Correction: Secondary Meningioma. Journal of Nuclear Medicine & Cortical Pathways. Journal of Child Neurology. - an age related baroreflex dysfunction. Defended Defended on the 17th of March 2015, University of with Parathyroid Carcinoma Mimicking Skeletal Hyperalgesia Phenotypes Exhibit Differences in Radiation Therapy. 2015;6(6):1-4. 2015;30(10):315-326. on the 12th of November 2015, University of Copenhagen. Metastases on 18F-FDG PET/CT. Diagnostics. Brain Activation during Noxious Stimulation. P L o Berg RMG, Plovsing RR, Bailey DM, Holstein- Dunkl V, Cleff C, Stoffels G, Judov N, Sarikaya- Copenhagen. Wulff S. PhD thesis. The connection between 2015;5(3):290-3. S One. 2015 May 16;10(5):e0128640. Rathlou N-H, Møller K. The Dynamic cerebral Seiwert S, Law I, Bøgeskov L, Nysom K, Andersen Cramer SP. PhD thesis. Permeability of the blood- dopamine D2 activity, reward disturbances and Andersen KF, Albrecht-Beste E, Berthelsen AK, Asghar MS, Pereira MP, Werner MU, Mårtensson J, autoregulatory adaptive response to noradrenaline SB, Steiger HJ, Fink GR, Reifenberger G, Shak brain barrier as measured by dynamic contrast- psychopathology. Defended on the 26th of February Loft A. Angiosarcoma of the Scalp: Metastatic Larsson HBW, Dahl JB. Secondary Hyperalgesia is attenuated during systemic inflammation in NJ, Coenen HH, Langen KJ, Galldiks N. The enhanced perfusion MRI. Defended on the 30th of 2015, University of Copenhagen. Pulmonary Cystic Lesions Initially Misinterpreted Phenotypes Exhibit Differences in Brain Activation humans. Clinical and Experimental Pharmacology usefulness of dynamic O-(2-18F-fluoroethyl)-L- June 2015, University of Copenhagen. as Benign Findings on 18F-FDG PET/CT. during Noxious Stimulation. P L o S One. & Physiology. 2015 Jul;42(7):740-6. tyrosine PET in the clinical evaluation of brain Knudsen A. PhD thesis. Mechanisms behind the Diagnostics. 2015;6(1):1-4. 2015;10(1):e0114840. Brinth LS, Pors K, Theibel AC, Latif T, Kjær A, tumors in children and adolescents. Journal of increased risk of cardiovascular disease in HIV- Patents Andersen JB, Henning WS, Lindberg U, Ladefoged Asmar A, Simonsen L, Asmar M, Madsbad S, Holst Mehlsen J. Baroreflex Sensitivity And Autonomic Nuclear Medicine. 2015 Jan;56(1):88-92. infected patients. Defended on the 24th of April Kjær A (with co-inventors). 177Lu labeled peptide for CN, Højgaard L, Greisen G, Law I. Positron JJ, Frandsen E, Moro C, Jonassen T, Bülow J. Renal Nervous System Function In Carotid Sinus Ebdrup BH, Raghava JM, Nielsen MØ, Rostrup 2015, University of Copenhagen. site-specific uPAR-targeting. EP-2846826 and US- emission tomography/magnetic resonance hybrid Extraction and Acute Effects of Glucagon-like Hypersensitivity. EC Cardiology. 2015;2(1):50-59. 2. E, Glenthøj BY. Frontal fasciculi and psychotic Lindberg U. PhD thesis. Measurement of the 20150132219. March 18 and May 14, 2015. scanner imaging of cerebral blood flow using peptide-1 on Central and Renal Hemodynamics Cederkrantz E, Andersson H, Bernhardt P, Bäck T, symptoms in antipsychotic-naïve patients with neurovascular coupling in the healthy and Kjær A (with co-inventors). Positron emitting 15O-water positron emission tomography and in Healthy Men. American Journal of Physiology: Hultborn R, Jacobsson L, Jensen H, Lindegren S, schizophrenia before and after six weeks of diseased brain using fMRI. Defended on 11th of radionuclide labeled peptides for human uPAR arterial spin labeling magnetic resonance imaging Endocrinology and Metabolism. 2015 Feb Ljungberg M, Magnander T, Palm S, Albertsson selective dopamine D2/3 receptor blockade. June 2015, University of Copenhagen. PET imaging. EP-2928505. October 14, 2015. in newborn piglets. Journal of cerebral blood flow 10;308(8):E641-9. P. Absorbed Doses and Risk Estimates of (211) Journal of Psychiatry and Neuroscience. 2015;41(1). Li F. PhD thesis. 64Cu-ATSM PET for hypoxia imaging Kjær A (with co-inventors). Loading technique for and metabolism. 2015 Nov;35(11):1703-10. Aznar MC, Maraldo MV, Schut DA, Lundemann M, At-MX35 F(ab’)2 in Intraperitoneal Therapy of El-Galaly TC, Pedersen MB, Hutchings M, Mylam KJ,

- kinetic modelling and evaluation using pO2 preparing radionuclide containing nanoparticles. Andrésdóttir G, Jensen ML, Carstensen B, Parving Brodin NP, Vogelius IR, Berthelsen AK, Specht Ovarian Cancer Patients. International Journal of Madsen J, Gang AO, Bøgsted M, de Nully Brown P, measurements. Defended on the 30th of June 2015, US-20150202336. July 13, 2015. HH, Hovind P, Hansen TW, Rossing P. Improved L, Petersen PM. Minimizing late effects for Radiation: Oncology - Biology - Physics. 2015 Nov Loft A, Nielsen AL, Hendel HW, Iyer V, Gormsen University of Copenhagen. Olesen OV. Method for Surface Scanning in Medical prognosis of diabetic nephropathy in type 1 patients with mediastinal Hodgkin lymphoma: 1;93(3):569-76. LC. Utility of interim and end-of-treatment PET/CT Nedergaard MK. PhD thesis. 18F-FET PET to monitor Imaging and Related Apparatus. WO2015071369 . diabetes. Kidney Int. 2015 Feb;87(2):417-26. deep inspiration breath-hold, IMRT, or both? Christensen TE, Ahtarovski KA, Bang LE, Holmvang in peripheral T-cell lymphomas: A review of 124 tumour response development and assess May 21, 2015. Aneheim E, Albertsson P, Bäck T, Jensen H, International Journal of Radiation: Oncology - L, Søholm H, Ghotbi AA, Andersson H, Vejlstrup patients. American Journal of Hematology. 2015 treatment response in Glioblastoma Multiforme: Palm S, Lindegren S. Automated astatination Biology - Physics. 2015 May 1;92(1):169-74. N, Ihlemann N, Engstrøm T, Kjær A, Habak P. Nov;90(11):975-80. Multimodal imaging in orthotopic xenograft of biomolecules - a stepping stone towards Bailey DL, Pichler BJ, Gückel B, Barthel H, Beer AJ, Basal hyperaemia is the primary abnormality El-Galaly TC, Villa D, Alzahrani M, Hansen JW, models. Defended on the 30th of March 2015, Publications multicenter clinical trials. Scientific Reports. Bremerich J, Caemin J, Drzezga A, Franzius C, of perfusion in Takotsubo cardiomyopathy: a Sehn LH, Wilson D, de Nully Brown P, Loft A, University of Copenhagen. Andersen KF, Fuglo HM, Rasmussen SH, Petersen 2015;5:12025. Goh V, Hartenbach M, Lida H, Kjær A, la Fugère quantitative cardiac perfusion positron emission Iyer V, Johnsen HE, Savage KJ, Connors JM, Olsen IH. PhD thesis. Studies of neuroendocrine MM, Loft A. Volume-Based 18F-FDG PET/CT Aneheim E, Foreman MRS, Jensen H, Lindegren C, Ladefoged CN, Law I, Nikolaou K, Quick HH, tomography study. European Heart Journal Hutchings M. Outcome prediction by extranodal carcinomas and goblet cell carcinoids. Defended Imaging Markers Provide Supplemental Prognostic S. N-[2-(maleimido)ethyl]-3-(trimethylstannyl) Sabri O, Schäfer M, Wehrl HF, Beyer T. Combined Cardiovascular Imaging. 2015 Oct;16(10):1162-9. involvement, IPI, R-IPI, and NCCN-IPI in the on the 15th of December 2015, University of Information to Histologic Grading in Patients With benzamide, a molecule for radiohalogenation PET/MRI: Multi-modality Multi-parametric Cramer SP, Modvig S, Simonsen HJ, Frederiksen JL, PET/CT and rituximab era: A Danish-Canadian Copenhagen. High-Grade Bone or Soft Tissue Sarcoma. Medicine of proteins and peptides. Applied radiation and Imaging Is Here. Molecular Imaging and Biology. Larsson HBW. Permeability of the blood-brain study of 443 patients with diffuse-large B-cell Pfeifer AK. PhD thesis. Theranostics in (Baltimore). 2015 Dec;94(51):e2319. isotopes : including data, instrumentation and 2015 Oct;17(5):595-608. barrier predicts conversion from optic neuritis lymphoma. American Journal of Hematology. 2015 neuroendocrine tumors: evaluation of a new PET Andersen KF, Fuglo HM, Rasmussen SH, Petersen methods for use in agriculture, industry and Bandel I, Bungum M, Richtoff J, Malm J, Axelsson to multiple sclerosis. Brain. 2015 Jul 17;138(Pt. Nov;90(11):1041-6. tracer & peptide receptor radionuclide, therapy MM, Loft A. Semi-Quantitative Calculations of medicine. 2015 Feb;96:1-5. J, Pedersen HS, Ludwicki JK, Czaja K, Hernik 9):2571-83. Erlandsson M, Nielsen CH, Jeppesen TE, Kristensen

60 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 61 J, Petersen LC, Madsen J, Kjær A. Synthesis and Tomography Study. Biological Psychiatry. 2015 Oct 13C-Pyruvate Magnetic Resonance Spectroscopic microspheres. Journal of Biomedical Graphics and Based In Vivo Evaluation of 64Cu Labelled Jespersen JG, Mikkelsen UR, Nedergaard A, characterization of 18F-labeled active site inhibited 15;78(8):534-543. Imaging (hyperPET): Mismatch Demonstrates that Computing. 2015;33-39. Nanodiscs in Tumor Bearing Mice. P L o S One. Thorlund JB, Schjerling P, Suetta C, Christensen factor VII (ASIS). Journal of Labelled Compounds Gagnon L, Ismaili ARA, Ptito M, Kupers R. Superior FDG may not Always Reflect the Warburg Effect. Henriksen JR, Petersen AL, Hansen AE, Frankær 2015;10(7):e0129310. PA, Aagaard P. Alterations in molecular muscle and Radiopharmaceuticals. 2015 May 15;58(5):196- orthonasal but not retronasal olfactory skills Diagnostics. 2015;5(3):287-9. CG, Harris P, Elema DR, Kristensen AT, Kjær A, Haahr ME, Hansen DL, Fisher PM, Svarer C, mass regulators after 8 days immobilizing Special 201. in congenital blindness. P L o S One. Gutte Borgwardt H, Hansen AE, Larsen M, Rahbek S, Andresen TL. Remote Loading of 64Cu(2+) into Stenbæk DS, Madsen K, Madsen J, Holst JJ, Baaré Forces mission. Scand J mass regulators after 8 Fisher PM, Holst KK, Adamsen D, Klein AB, Frokjaer 2015;10(3):e0122567. Henriksen ST, Johannesen HH, Ardenkjær-Larsen Liposomes without the Use of Ion Transport WF, Højgaard L, Almdal T, Knudsen GM. Central days immobilizing Special Forces mission. Scand J VG, Jensen PS, Svarer C, Gillings N, Baare WF, Ghotbi AA, Sander M, Køber L, Philbert BT, J, Kristensen AT, Højgaard L, Kjær A. Simultaneous Enhancers. A C S Applied Materials and Interfaces. 5-HT neurotransmission modulates weight Med Sci Sports. 2015 Apr:25(2):175-83. Mikkelsen JF, Knudsen GM. BDNF Val66met and Gustafsson F, Hagemann C, Kjær A, Jacobsen Hyperpolarized 13C-Pyruvate MRI and 18F-FDG 2015 Oct 21;7(41):22796-806. loss following gastric bypass surgery in obese Jølck RI, Rydhög JS, Christensen AN, Hansen AE, 5-HTTLPR polymorphisms predict a human in PK. Optimal Cardiac Resynchronization Therapy PET (HyperPET) in 10 Dogs with Cancer. Journal Herth MM, Lykke Andersen V, Hansen HD, Stroth individuals. The Journal of Neuroscience. 2015 Apr Bruun LM, Schaarup-Jensen H, von Wenck AS, vivo marker for brain serotonin levels. Human Pacing Rate in Non-Ischemic Heart Failure of nuclear medicine. 2015 Nov;56(11):1786-92. N, Volk B, Lehel S, Dyssegaard A, Ettrup A, 8;35(14):5884-9. Børresen B, Kristensen AT, Clausen MH, Kjær Brain Mapping. 2015 Jan;36(1):313-23. Patients: A Randomized Crossover Pilot Trial. Hagemann CE, Ghotbi AA, Kjær A, Hasbak Svenningsson P, Knudsen GM, Kristensen JL. Ilett EE, Langer SW, Olsen IH, Federspiel B, Kjær A, Conradsen K, Larsen R, af Rosenschöld PM, Fjære E, Andersen C, Myrmel LS, Petersen RK, P L o S One. 2015;10(9):e0138124. P. Quantitative myocardial blood flow with Evaluation of 3-Ethyl-3-(phenylpiperazinylbutyl) A, Knigge U. Neuroendocrine Carcinomas of the Andresen TL. Injectable Colloidal Gold for Use Hansen JB, Tastesen HS, Mandrup-Poulsen T, Goetze JP, Johnsen AH, Kistorp C, Gustafsson Rubidium-82 PET: a clinical perspective. American oxindoles as PET Ligands for the Serotonin 5-HT₇ Gastroenteropancreatic System: A Comprehensive in Intrafractional 2D Image-Guided Radiation Brünner N, Kristiansen K, Madsen L, Rømer MU. F, Johnbeck CB, Rehfeld JF. Cardiomyocyte Journal of Nuclear Medicine and Molecular Receptor: Synthesis, Pharmacology, Radiolabeling, Review. Diagnostics. 2015;5(2):119-76. Therapy. Advanced Healthcare Materials. 2015 Tissue Inhibitor Of Matrix Metalloproteinase-1 expression and cell-specific processing of Imaging. 2015;5(5):457-68. and in Vivo Brain Imaging in Pigs. Journal of Iversen KD, Ptito M, Møller P, Kupers R. Enhanced Apr 22;4(6):856-63. Is Required for High-Fat Diet-Induced Glucose procholecystokinin. The Journal of biological Hansen HV, Loft A, Berthelsen AK, Christensen IJ, Medicinal Chemistry. 2015 Apr 23;58(8):3631-6. chemosensory detection of negative emotions Kamstrup MR, Gniadecki R, Iversen L, Skov L, Intolerance and Hepatic Steatosis in Mice. P L o S chemistry. 2015 Mar 13;290(11):6837-43. Høgdall C, Engelholm SA. Survival outcomes in Holmager P, Schmidt U, Mark P, Andersen U, in congenital blindness. Neural Plasticity. Petersen PM, Loft A, Specht L. Low-dose (10-Gy) One. 2015;10(7):e0132910. Greve AM, Bang CN, Berg RMG, Egstrup K, Rossebø patients with cervical cancer after inclusion of Dominguez Vall-Lamora MH, Raymond I, 2015;2015:469750. total skin electron beam therapy for cutaneous Fledelius HC, Korsholm K, Law I. Functional PET AB, Boman K, Nienaber CA, Ray S, Gohlke-Baerwolf PET/CT in staging procedures. European journal Zerahn B, Nygaard B, Kistorp C, Faber J. Long- Jensen RR, Benjaminsen C, Larsen R, Olesen OV. T-cell lymphoma: an open clinical study and Scan in four Patients with higher order neglect-like C, Nielsen OW, Okin PM, Devereux RB, Køber L, of Nuclear Medicine and Molecular Imaging. 2015 term L-Triiodothyronine (T3) treatment in stable Brain Image Motion Correction: Impact of Incorrect pooled data analysis. International Journal of cognitive dysfunction associated to chiasm related Wachtell K. Resting heart rate and risk of adverse Nov;42(12):1833-9. systolic heart failure patients: a randomised, Calibration and Noisy Tracking. I Image Analysis: Radiation: Oncology - Biology - Physics. 2015 pathology. Open Journal of Ophthalmology. cardiovascular outcomes in asymptomatic aortic Hansen HD, Lykke Andersen V, Lehel S, Magnussen double-blind, cross-over, placebo-controlled 19th Scandinavian Conference, SCIA 2015:159-68. May 1;92(1):138-43. 2015;5(2):54-60. stenosis: the SEAS study. International Journal of JH, Dyssegaard A, Stroth N, Kristensen JL, intervention study. Clinical Endocrinology. 2015 Jensen P, Feng L, Law I, Svarer C, Knudsen GM, Keller SH, Hansen C, Hansen C, Littrup Andersen F, Fischer PM, Haahr ME, Jensen CG, Frokjaer VG, Cardiology. 2015 Feb 1;180:122-8. Knudsen GM, Herth MM. Labeling and Dec;83(6):931-7. Mikkelsen JD, de Nijs R, Larsen VA, Dyssegaard Ladefoged C, Svarer C, Kjær A, Højgaard L, Law Siebner HR, Knudsen GM. Fluctuations in 11C- Gutte Borgwardt H, Hansen AE, Henriksen ST, preliminary in vivo evaluation of the 5-HT(7) Hougaard A, Amin FM, Hoffmann MB, Larsson A, Thomsen G, Fischer W, Guilloteau D, Pinborg I, Henriksen OM, Hansen AE. Motion correction SB207145 PET binding associated with change Johannesen HH, Ardenkjaer-Larsen J, Vignaud A, receptor selective agonist [11C]E-55888. Bioorganic HBW, Magon S, Sprenger T, Ashina M. Structural LH. TSPO Imaging in Glioblastoma Multiforme: in simultaneous PET/MR brain imaging using in threat-related amygdala reactivity in humans. Hansen AE, Børresen B, Klausen TL, Wittekind & Medicinal Chemistry Letters. 2015 May gray matter abnormalities in migraine relate to A Direct Comparison Between 123I-CLINDE sparsely sampled MR navigators: a clinically Neuropsychopharmacology. 2015 May;40(6):1510- AM, Gillings N, Kristensen AT, Clemmensen A, 1;25(9):1901-4. headache lateralization, but not aura. Cephalalgia: SPECT, 18F-FET PET, and Gadolinium-Enhanced feasible tool. EJNMMI Physics. 2015 Dec;2(1):14. 8. Højgaard L, Kjær A. Simultaneous hyperpolarized Hansen AE, Petersen AL, Henriksen JR, Boerresen an international journal of headache. 2015 MR Imaging. Journal of Nuclear Medicine. 2015 Kjær A, Knigge U. Use of radioactive substances Fosbøl MØ, Zerahn B. Contemporary methods 13C-pyruvate MRI and 18F-FDG-PET in cancer B, Rasmussen P, Elema DR, Rosenschöld PM, Jan;35(1):3-9. Sep;56(9):1386-90. in diagnosis and treatment of neuroendocrine of body composition measurement. Clinical (hyperPET): feasibility of a new imaging concept Kristensen AT, Kjær A, Andresen TL. Positron Hougaard A, Jensen BH, Amin FM, Rostrup E, Jensen MM, Kjær A. Monitoring of anti-cancer tumors. Scandinavian journal of gastroenterology. Physiology and Functional Imaging. 2015 using a clinical PET/MRI scanner. American Emission Tomography Based Elucidation of the Hoffmann MB, Ashina M. Cerebral Asymmetry of treatment with 18F-FDG and 18F-FLT PET: a 2015 Jun;50(6):740-747. Mar;35(2):81-97. Journal of Nuclear Medicine and Molecular Enhanced Permeability and Retention Effect in fMRI-BOLD Responses to Visual Stimulation. comprehensive review of pre-clinical studies. Klausen TL, Mortensen J, de Nijs R, Andersen FL, Frederiksen KS, Hasselbalch S, Law I, Højgaard Imaging 2015;5(1):38-45. Dogs with Cancer Using Copper-64 Liposomes. P L o S One. 2015;10(5):e0126477. American Journal of Nuclear Medicine and Højgaard L, Beyer T, Holm S. Intravenous contrast- L, Waldemar G. Biomarkører ved diagnostik af Gutte Borgwardt H, Hansen AE, Johannesen A C S Nano. 2015 Jul 28;9(7):6985-95. Hougaard A, Lindberg U, Arngrim N, Larsson HBW, Molecular Imaging. 2015;5(5):431-56. enhanced CT can be used for CT-based attenuation Alzheimers sygdom i tidlig fase: Biomarkers for HH, Clemmensen AE, Ardenkjær-Larsen JH, Heine L, Bahri MA, Cavaliere C, Soddu A, Reislev Olesen J, Amin FM, Haddock BT. Evidence of a Jensen BH, Hougaard A, Amin FM, Larsson HBW, correction in clinical 111In-octreotide SPECT/CT. early diagnosis of Alzheimer’s disease. Ugeskrift Nielsen CH, Kjær A. The use of dynamic nuclear NL, Laureys S, Pitto M, Kupers R. Corrigendum: Christmas spirit network in the brain: functional Ashina M. Structural asymmetry of cortical visual EJNMMI Physics. 2015 Dec;2(1):3. for Laeger. 2015 jun 8;177(24):V12140684. polarization 13C-pyruvate MRS in cancer. American Prevalence of increases in functional connectivity MRI study. B M J (Online). 2015;351:h6266. areas is related to ocular dominance. Neuroreport. Knudsen A, Hag AMF, Loft A, von Benzon E, Keller Frokjaer VG, Pinborg AB, Holst KK, Overgaard A, Journal of Nuclear Medicine and Molecular in visual, somatosensory and language areas in Hougaard A, Amin FM, Magon S, Sprenger T, 2015 Dec 2;26(17):1071-6. SH, Møller HJ, Lebech AM, Ripa RS, Kjær A. HIV Henningsson S, Heede M, Larsen EC, Jensen PS, Imaging. 2015;5(5):548-60. congenital blindness. Frontiers in Neuroanatomy. Rostrup E, Ashina M. No abnormalities of Jensen AS, Idorn L, Thomsen C, von der Recke infection and arterial inflammation assessed by Agn M, Nielsen AP, Stenbæk DS, da Cunha-Bang Gutte Borgwardt H, Hansen AE, Larsen M, Rahbek S, 2015:9:106. intrinsic brain connectivity in the interictal phase P, Mortensen J, Sørensen KE, Thilén U, Nagy 18F-fluorodeoxyglucose (FDG) positron emission S, Lehel S, Siebner HR, Mikkelsen JD, Svarer Johannesen HH, Ardenkjaer-Larsen J, Kristensen Henning W, Andersen JB, Højgaard L, Greisen of migraine with aura. European journal of E, Kofoed KF, Ostrowski SR, Søndergaard L. tomography (PET): A prospective cross-sectional C, Knudsen GM. Role of Serotonin Transporter AT, Højgaard L, Kjær A. In Vivo Phenotyping of G, Law I, Thorseth A, Christensen AN. A new neurology. 2015 Jan 9;22:702-10. Prevalence of cerebral and pulmonary thrombosis study. Journal of Nuclear Cardiology: official Changes in Depressive Responses to Sex-Steroid Tumor Metabolism in a Canine Cancer Patient with self-made digital slide scanner and microscope Huda P, Binderup T, Pedersen MC, Midtgaard SR, in patients with cyanotic congenital heart disease. publication of the American Society of Nuclear Hormone Manipulation: A Positron Emission Simultaneous 18F-FDG-PET and Hyperpolarized for imaging and quantification of fluorescent Elema DR, Kjær A, Jensen M, Arleth L. PET/CT Heart. 2015 Oct 1;101(19):1540-6. Cardiology. 2015;22(2):e372-80.

62 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 63 Knudsen A, Christensen TE, Ghotbi AA, Hasbak P, Hegen H, Rauch S, D’Alfonso S, Alvarez-Cermeno Ladefoged CN, Benoit D, Law I, Holm S, Kjær Londero SC, Krogdahl A, Bastholt L, Overgaard B. Treating Hypothyroidism with Thyroxine/ chemotherapy in patients with diffuse large B-cell Lebech A-M, Kjær A, Ripa RS. Normal Myocardial JC, Kleinová P, Horáková D, Roesler R, Lauda A, Højgaard L, Hansen AE, Andersen FL. J, Pedersen HB, Hahn CH, Bentzen J, Schytte S, Triiodothyronine Combination Therapy in lymphoma: Results of a Nordic/US intergroup Flow Reserve in HIV-Infected Patients on Stable F, Llufriu S, Avsar T, Uygunoglu U, Altintas A, Region specific optimization of continuous Christiansen P, Gerke O, Godballe C. Papillary Denmark: Following Guidelines or Following study. Leukemia and Lymphoma. 2015;56(7):2005-12. Antiretroviral Therapy: A Cross-Sectional Study Saip S, Menge T, Rajda C, Bergamaschi R, Moll linear attenuation coefficients based on UTE thyroid carcinoma in Denmark, 1996-2008: Trends?. European Thyroid Journal. 2015 Møller UK, Jensen LT, Mosekilde L, Rejnmark L. Using Rubidium-82 PET/CT. Medicine. 2015 N, Khalil M, Marignier R, Dujmovic I, Larsson H, (RESOLUTE): application to PET/MR brain Outcome and evaluation of established prognostic Sep;4(3):174-80. Effects of Adding Chymosin to Milk on Calcium Oct;94(43):e1886. Malmestrom C, ScarpiniE, Fenoglio C, Wergeland imaging. Physics in Medicine and Biology. 2015 scoring systems in a prospective national cohort. Mikati AG, Khanna O, Zhang L, Girard R, Shenkar R, Homeostasis: A Randomized, Double-Blind, Knudsen A, Malmberg CAE, Kjær A, Lebech A-M. S, Laroni A, Annibali V, Romano S, Martinez AD, Oct 21;60(20):8047-65. Danish Thyroid Cancer Group – DATHYRCA (part Guo X, Shah A, Larsson HB, Tan H, Li L, Wishnoff Cross-Over Study. Calcified Tissue International. Low prevalence of peripheral arterial disease in Carra A, Salvetti M, Uccelli A, Torkildsen Ø, Myhr Ladefoged CN, Hansen AE, Keller SH, Fischer BM, of the DAHANCA organization). Thyroid. 2015 MS, Shi C, Christoforidis GA, Awad IA. Vascular 2015;96(2):105-112. a cross-sectional study of Danish HIV-infected KM, Galimberti D, Rejdak K, Lycke J, Frederiksen Rasmussen JH, Law I, Kjær A, Højgaard L, Lauze Jan;25(1):78-84. permeability in cerebral cavernous malformations. Møller T, Lillelund C, Andersen C, Bloomquist patients. Infectious diseases. 2015;47(11):776-82. JL, Drulovic J, ConfavreuxC, Brassat D, Enzinger F, Beyer T, Andersen FL. Dental artifacts in the Lundberg H, Enevoldsen LH. Inflammation i en Journal of Cerebral Blood Flow and Metabolism. K, Christensen KB, Ejlertsen B, Nørgaard L, Konge L, Albrecht-Beste E, Nielsen MB. Ultrasound C, Fuchs S, Bosca I, Pelletier J, Picard C, Colombo head and neck region: implications for Dixon- bugvægsmeche. Ugeskrift for Laeger. 2015 Feb 2015 Oct;35(10):1632-9. Wiedenbein, Oturai P, Breitenstein U, Adamsen in Pre-Graduate Medical Education. Ultraschall in E, Franciotta D, Derfuss T, Lindberg R, Yaldizlil based attenuation correction in PET/MR. EJNMMI 16;177(8). Mohr M, Helge EW, Petersen LF, Lindenskov A, L. The challenge of preserving cardiorespiratory der Medizin. 2015 Jun;36(3):213-5. Ö, Vécsei L, Kieseier BC, Hartung HP, Villoslada Physics. 2015 Dec;2(1):8. Lykke Andersen V, Hansen HD, Herth MM, Weihe P, Mortensen J, Jørgensen NR, Krustrup fitness in physically inactive patients with colon Kornerup JS, Brodin P, Christensen C, Björk- P, Siva A, Saiz A, Tumani H, Havrdová, Villar Larsson HBW, Hansen TF. Dynamic Contrast- Dyssegaard A, Knudsen GM, Kristensen JL. P. Effects of soccer vs swim training on bone or breast cancer during adjuvant chemotherapy: a Eriksson T, Berthelsen AK, Borgwardt L, Munck LM, Leone M, Barizzone N, Deisenhammer F, Enhanced T1-Weighted MR Imaging. Perfusion 11C-labeling and preliminary evaluation of formation in sedentary middle-aged women. randomised feasibility study. BMJ Open Sport & af Rosenschöld P. Use of PET/CT instead of CT- Teunissen C, Montalban X, Tintoré M, Olsson T, Imaging in Clinical Practice: A Multimodality pimavanserin as a 5-HT2A receptor PET- European Journal of Applied Physiology. 2015 Exercise Medicine. 2015 Oct 1;1(1). only when planning for radiation therapy does Trojano M, Lehmann S, Castelnovo G, Lapin S, Approach to Tissue Perfusion Analysis. Wolters radioligand. Bioorganic & Medicinal Chemistry Dec;115(12):2671-9. Møller S, Lundemann M, Law I, Poulsen HS, Larsson not notably increase life years lost in children Hintzen R, Kappos L, Furlan R, Martinelle V, Comi Kluwer Health. 2015:121-148. Letters. 2015 Mar 1;25(5):1053-6. Morbelli S, Garibotto V, Van De Giessen E, Arbizu J, HBW, Engelholm SA. Early changes in perfusion being treated for cancer. Pediatric Radiology. 2015 G, Ramaqopalan SV, Giovanni G. Conversion from Larsson HBW, Hansen TF. Perfusion Imaging in Løkke A, Ahlbeck L, Bjermer L, Mortensen J, Chételat G, Drezgza A, Hesse S, Lammertsma AA, of glioblastoma during radio- and chemotherapy Apr;45(4):570-81. clinically isolated syndrome to multiple sclerosis: Clinical Practise: A Multimodality Approach to Østrem A, Pasternack I, Safioti G, Torvinen S. Law I, Pappata S, Payoux P, Pagani M. A Cochrane evaluated by T1-dynamic contrast enhanced Kornerup JS, Brodin NP, Björk-Eriksson T, A large multicentre study. Multiple Sclerosis. 2015 Tissue Perfusion Analysis. Dynamic Contrast- Expert Nordic perspectives on the potential of review on brain [¹⁸F]FDG PET in dementia: magnetic resonance imaging. Acta oncologica Christensen C, Berthelsen AK, Aznar MC, Jul;21(8):1013-24. Enhanced T1-weighted MR Imaging: Theory, novel inhalers to overcome unmet needs in the limitations and future perspectives. European (Stockholm, Sweden). 2015 Oct;54(9):1521-8. Hollensen C, Markova E, Munck af Rosenschöld P. Kvorning T, Kadi F, Schjerling P, Andersen M, Quantitative Aspects, and Practical Implementation. management of obstructive lung disease. European Journal of Nuclear Medicine and Molecular Nedergaard MK, Michaelsen SR, Urup T, Broholm PET/CT-guided treatment planning for paediatric Brixen K, Suetta C, Madsen K. The activity Wolters Kluwer Health. 2015:121-148. Clinical Respiratory Journal. 2015. 2:29445. Imaging. 2015 Sep;42(10):1487-91. H, El Ali H, Poulsen HS, Stockhausen MT, Kjær cancer patients: a simulation study of proton and of satellite cells and myonuclei following 8 Law I, Højgaard L. Brain tumours: other primary brain Malmberg C, Ripa RS, Johnbeck CB, Knigge U, Mortensen J. Assessing nodules detected in lung A, Lassen U. 18F-FET microPET and microMRI for conventional photon therapy. The British journal of weeks of strength training in young men with tumors, metastases and radiation injury. Clinical Langer SW, Mortensen J. Oturai P, Loft A, Hag cancer screening: the value of positron emission anti-VEGF and anti-PlGF response assessment Radiology. 2015 Mar;88(1047):20140586. suppressed testosterone levels. Acta Physiologica. molecular anatomic imaging - PET/CT, PET/MR AM, Kjær A. 64Cu-DOTATATE for Noninvasive tomography. European Respiratory Journal. 2015 in an orthotopic murine model of human Korsholm K, Feldt-Rasmussen U, Granqvist H, 2015;213(3):676-87. and SPECT/CT. Wolters Kluwer Health. 2015:169-79. Assessment of Atherosclerosis in Large Arteries Feb;45(2):314-6. glioblastoma. P L o S One. 2015;10(2):e0115315. Højgaard L, Bollinger B, Rasmussen AK, Law I. Kümler I, Balslev E, Poulsen TS, Nielsen SL, Law I, Borgwardt L, Højgaard L. Pediatric hybrid and Its Correlation with Risk Factors: Head- Munck Af Rosenschold P, Costa J, Engelholm SA, Nielsen SM, Vinter MD, Roed H, Sørensen T, Larsson Positron Emission Tomography and Magnetic Nygård SB, Rømer MU, Christensen IJ, Høgdall imaging of the brain. Clinical molecular anatomic to-Head Comparison with 68Ga-DOTATOC in Lundemann MJ, Law I, Ohlhues L, Engelholm HBW, Langkilde A, Frederiksen JL, Sellebjerg F. Resonance Imaging of the Brain in Fabry Disease: E, Moreira J, Nielsen DL, Brünner N, Stenvang imaging - PET/CT, PET/MR and SPECT/CT. 60 Patients. Journal of Nuclear Medicine. 2015 S. Impact of [18F]-fluoro-ethyl-tyrosine PET Cerebrospinal fluid levels of chitinase 3-like 1 and A Nationwide, Long-Time, Prospective Follow-Up. J. Topoisomerase-1 gene copy aberrations Wolters Kluwer Health. 2015:218-29. Dec;56(12):1895-900. imaging on target definition for radiation therapy neurofilament light chain predict multiple sclerosis P L o S One. 2015 Dec 2;10(12):e0143940. are frequent in patients with breast cancer. Li F, Jørgensen JT, Madsen J, Kjær A. Pharmacokinetic Mandøe MJ, Hansen KB, Hartmann B, Rehfeld JF, of high-grade glioma. Neuro-Oncology. 2015 development and disability after optic neuritis. Kristensen M, Pötzelsberger B, Scheiber P, Bergdahl International Journal of Cancer. 2015 Apr Analysis of 64Cu-ATSM Dynamic PET in Holst JJ, Hansen HS. The 2-monoacylglycerol May;17(5):757-63. Multiple Sclerosis. 2015 Feb 19;1761-70. A, Hansen CN, Andersen JL, Narici M, Salvioli 8;137(8):2000-6. Human Xenograft Tumors in Mice. Diagnostics. moiety of dietary fat appears to be responsible Munkholm M, Nielsen KG, Mortensen J. Clinical Nielsen CH, Jensen MM, Kristensen L, Dahlman S, Conte M, Müller E, Dela F. Alpine Skiing With la Cour JL, Jensen LT, Vej-Hansen A, Nygaard 2015;5(2):96-112. for the fat-induced release of GLP-1 in humans. value of measurement of pulmonary radioaerosol A, Fröhlich C, Jacobsen HJ, Poulsen TT, Lantto J, total knee ArthroPlasty (ASWAP): metabolism, B. Radioiodine therapy increases the risk Lindegren S, Andrade LNS, Bäck T, Machado CML, The American Journal of Clinical Nutrition. 2015 mucociliary clearance in the work up of primary Horak ID, Kragh M, Kjær A. In vivo imaging of inflammation, and skeletal muscle fiber of cerebrovascular events in hyperthyroid Horta BB, Buchpiguel C, Moro AM, Okamoto Sep;102(3):548-55. ciliary dyskinesia. EJNMMI research. 2015 therapy response to a novel pan-HER antibody characteristics. Scandinavian Journal of Medicine and euthyroid patients. European journal of OK, Jacobsson L, Cederkrantz E, Washiyama Mark PD, Andreassen M, Petersen CL, Kjær A, Faber Dec;5(1):118. mixture using FDG and FLT positron emission & Science in Sports. 2015 Aug;25 Suppl 2:40-8. endocrinology2015 Jun;172(6):771-8. K, Aneheim E, Palm S, Jensen H, Tuma MCB, J. Treatment of subclinical hyperthyroidism: effect Mylam KJ, Kostakoglu L, Hutchings M, Coleman tomography. OncoTarget. 2015 Nov 10;6(35):37486-99. Kuhle J, Disanto G, Dobson R, Adiutori R, Bianchi Ladefoged CN, Littrup Andersen F, Keller SH, Chammas R, Hultborn R. Binding Affinity, on left ventricular mass and function of the heart M, Lamonica D, Czuczman MS, Diehl LF, Nielsen Olsen IH, Holt NKS, Langer SW, Hasselby JP, L, Topping CJ, Bestwick JP, Meier UC, Marta M, Beyer T, Law I, Højgaard L, Darkner S, Lauze Specificity and Comparative Biodistribution using magnetic resonance imaging technique. AL, Jensen P, Loft A, Hendel HW, Iyer V, Leppä Grønbæk H, Hillingsø J, Mahmoud M, Ladekarl Dalla Costa G, Runia T, Evdoshenko E, Lazareva F. Automatic correction of dental artifacts in of the Parental Murine Monoclonal Antibody Endocrine Connections. 2015 Mar;4(1):37-42. S, Jyrkkiö S, Holte H, Eriksson M, Gillstrøm D, M, Iversen LH, Kjær A. Goblet cell carcinoids: N, Thouvenot E, Iaffaldano P, Direnzo V, Khademi PET/MRI. Journal of Medical Imaging. 2015 MX35 (Anti-NaPi2b) and Its Humanized Version Michaelsson LF, Medici BB, la Cour JL, Selmer C, Hansen PB, Seppänen M, Hjorthaug K, Brown P de characteristics of a danish cohort of 83 patients. P M, Piehl F, Comabella M, Sombekke M, Killestein J, Apr;2(2):024009. Rebmab200. P L o S One. 2015;10(5):e0126298. Røder M, Perrild H, Knudsen N, Faber J, Nygaard N, Pedersen LM. FDG-PET/CT after one cycle of L o S One. 2015;10(2):e0117627. Olsson A, Oturai

64 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 65 DB, Sørensen PS, Oturai PS, Oturai AB. Short- Petersen PM, Aznar MC, Berthelsen AK, Loft A, Ricardi U, Specht L, Versari A, Berthelsen AK. FDG- Based Antineoplastics: Solid Phase Radiosynthesis, EJ, Wojtkiewicz GR, Iwamoto Y, Tang J, Pereaz- term, high-dose glucocorticoid treatment does Schut DA, Maraldo M, Josipovic M, Klausen PET and radiotherapy in lymphoma. Clinical and PET and ex Vivo Evaluation of Antitumor Agent Medina C, Mani V, Ishino S, Johnbeck CB, Knigge not contribute to reduced bone mineral density in TL, Andersen FL, Specht L. Prospective phase II Translational Imaging. 2015;3:321-330. [(45)Ti](salan)Ti(dipic). Journal of Medicinal U, Fayad ZA, Libby P, Weissleder R, Tawakol patients with multiple sclerosis. Multiple Sclerosis. trial of image-guided radiotherapy in Hodgkin Ripa RS, Kjær A. Imaging atherosclerosis with Chemistry. 2015 Sep 24;58(18):7591-5. A, Dubey S, Belanger AP, Di Carli MF, Swieski 2015 Oct;21(12):1557-65. lymphoma: Benefit of deep inspiration breath- hybrid positron emission tomography/ Slatore CG, Horeweg N, Jett JR, Midthun DE, Powell FK, Kjær A, Mulder W, Nahrendorf M. Imaging Osler M, Rostrup E, Nordentoft M, Lykke Mortensen hold. Acta Oncologica. 2015 Jan;54(1):60-6. magnetic resonance imaging. BioMed Research CA, Wiener RS, Wisnivesky JP, Gould MK. An Macrophage and Hematopoietic Progenitor E, Bruunsgaard H, Fagerlund B. Influence of early Pfeifer A, Knigge U, Binderup T, Mortensen J, Oturai International. 2015;2015:914516. Official American Thoracic Society Research Proliferation in Atherosclerosis. Circulation life characteristics on psychiatric admissions and P, Loft A, Berthelsen AK, Langer SW, Rasmussen, Ripa RS, Hag AM, Knudsen A, Loft A, Specht L, Kjær Statement: A Research Framework for Pulmonary Research. 2015 Oct 23;117(10):835-45. impact of psychiatric disease on inflammatory Elema D, von Benzon E, Højgaard L, Kjær A. 64Cu- A. 18F-FDG PET imaging in detection of radiation- Nodule Evaluation and Management. American Zornhagen KW, Hansen AE, Oxboel J, Clemmensen biomarkers and survival: a Danish cohort study. DOTATATE PET for Neuroendocrine Tumors: induced vascular disease in lymphoma survivors. Journal of Respiratory and Critical Care Medicine. AE, El Ali HH, Kristensen AT, Kjær A. Micro World Psychiatry. 2015 Oct;14(3):364-5. A Prospective Head-to-Head Comparison with American Journal of Nuclear Medicine and 2015 Aug 15;192(4):500-14. Regional Heterogeneity of 64Cu-ATSM and 18F-FDG Oyen WJG, Sundram F, Haug AR, Kalevi K, 111In-DTPA-Octreotide in 112 Patients. Journal of Molecular Imaging. 2015;5(4):408-15. Uhlving HH, Andersen CB, Christensen IJ, Gormsen Uptake in Canine Soft Tissue Sarcomas: Relation to Lewington V, Mäenpaä H, Mortensen J, Mottaghy Nuclear Medicine. 2015 Jun;56(6):847-854. Saghir Z, Dirksen A, Ashraf H, Bach KS, Brodersen M, Pedersen KD, Buchvald F, Heilmann C, Nielsen Cell Proliferation, Hypoxia and Glycolysis. P L o S F, Ciefolini I, O’Sullivan JM, Wyndaele D. Rasmussen JH, Vogelius IR, Fischer BM, Friborg J, J, Clementsen PF, Døssing M, Hansen H, Kofoed KG, Mortensen J, Moser C, Sengeløv H, Müller KG. One. 2015;10(10):e0141379. Radium-223 Dichloride (Ra-223) for the Treatment Aznar MC, Persson GF, Håkansson K, Kristensen KF, Larsen KR, Mortensen J, Rasmussen JF, Biopsy-verified bronchiolitis obliterans and other Zornhagen KW, Clausen M, Hansen AE, Law I, of Metastatic Castration-resistant Prostate Cancer: CA, Bentzen SM, Specht L. Prognostic value of Thomsen LH, Wille MM, Seersholm N, Skov BG, noninfectious lung pathologies after allogeneic McEvoy F, Engelholm SA, Kjær A, Kristensen AT. Optimizing Clinical Practice in Nuclear Medicine 18F-fludeoxyglucose uptake in 287 patients with Thorsen H, Tønnesen P, Pedersen JH. Screening hematopoietic stem cell transplantation. Biology Use of Molecular Imaging Markers of Glycolysis, Centers. The Journal of Oncopathology. 2015;1-25. head and neck squamous cell carcinoma. Head & for lungecancer med lavdosis-CT - danske og of Blood and Marrow Transplantation. 2015 Hypoxia and Proliferation (18F-FDG, 64Cu-ATSM Paulsen IF, Chakera AH, Schmidt G, Drejøe J, Klyver Neck. 2015 Sep;37(9):1274-81. udenlandske resultater. Ugeskrift for Læger. Mar;21(3):531-8. and 18F-FLT) in a Dog with Fibrosarcoma: The H, Oturai PS, Hesse, Drzewiecki K, Mortensen Rasmussen JH, Vogelius IR, Aznar MC, Fischer BM, 2015;177(5):440-443. V05140283. Vervaat FE, Christensen TE, Smeijers L, Holmvang Importance of Individualized Treatment Planning J. Radionuclide leakage monitoring during Christensen CB, Friborg J, Loft A, Kristensen CA, Saghir Z, Dirksen A, Ashraf H, Bach KS, Brodersen L, Hasbak P, Szabó BM, Widdershoven JW, and Monitoring. Diagnostics. 2015;5(3):372-82. hyperthermic isolated limb perfusion for treatment Bentzen SM, Specht L. Spatio-temporal stability J, Clementsen PF, Døssing M, Hansen H, Kofoed Wagner GS, Bang LE, Gorgels AP. Is it possible to Zornhagen KW, Kristensen AT, Hansen AE, Oxboel of local melanoma metastasis in an extremity. Clinical of pre-treatment 18F-Fludeoxyglucose uptake KF, Larsen KR, Mortensen J, Rasmussen JF, differentiate between Takotsubo cardiomyopathy J, Kjær A. Selection of suitable reference genes Physiology and Functional Imaging. 2015;35(4):301-5. in head and neck squamous cell carcinomas Thomsen LH, Wille MMW, Seersholm N, Skov BG, and acute anterior ST-elevation myocardial for normalization of genes of interest in canine Pedersen SF, Sandholt BV, Keller SH, Hansen AE, sufficient for dose painting. Acta Oncologica 2015 Thorsen H, Tønnesen P, Pedersen JH. Screening infarction? Journal of Electrocardiology. 2015 Mar soft tissue sarcomas using quantitative real- Clemmensen AE, Sillesen H, Højgaard L, Ripa RS, Oct;54(9):1416-22. for lungecancer med lavdosis-CT kræver grundige 31;48(4):512-9. time polymerase chain reaction. Veterinary and Jaer A. 64Cu-DOTATATE PET/MRI for Detection of Rasmussen JH, Fischer BM, Aznar MC, Hansen overvejelser. Ugeskrift for Læger. 2015;177(5):436-439. Willowson KP, Tapner M, Bailey DL, QUEST Comparative Oncology. 2015 Dec;13(4):485-93. Activated Macrophages in Carotid Atherosclerotic AE, Vogelius IR, Löfgren J, Andersen FL, Loft A, Schjoeth-Eskesen C, Hansen PR, Kjær A, Gillings Investigator Team. A multicentre comparison of Plaques: Studies in Patients Undergoing Kjær A, Højgaard L, Specht L. Reproducibility of N. Efficient regioselective ring opening of activated quantitative 90Y PET/CT for dosimetric purposes Endarterectomy. Arteriosclerosis, Thrombosis and 18F-FDG PET uptake measurements in head and aziridine-2-carboxylates with 18F-Fluoride. after radioembolization with resin microspheres: As in previous reports we have listed scientific papers Vascular Biology. 2015 Jul;35(7):1696-703. neck squamous cell carcinoma on both PET/CT ChemistryOpen. 2015 Feb;4(1):65-71. The QUEST Phantom Study. European Journal of only and not the many abstracs and proceedings from the Pedraz-Cuesta E, Christensen S, Jensen AA, Jensen and PET/MR. The British Journal of Radiology. Schjoeth-Eskesen C, Nielsen CH, Heissel S, Højrup Nuclear Medicine and Molecular Imaging. 2015 department. NF, Bunch L, Romer MU, Brünner N, Stenvang 2015 Apr;88(1048):20140655. P, Hansen PR, Gillings N, Kjær A. 64Cu-labelled Jul;42(8):1202-22. J, Pedersen SF. The glutamate transport inhibitor Rasmussen GB, Vogelius IR, Rasmussen JH, trastuzumab: optimisation of labelling by DOTA Wilm J, Olesen OV, Reinhold Paulsen R, Larsen DL-Threo-β-Benzyloxyaspartic acid (DL-TBOA) Schumaker L, Ioffe O, Cullen K, Fischer and NODAGA conjugation and initial evaluation R. Correction of Motion Artifacts for Real- differentially affects SN38- and oxaliplatin-induced BM, Therkildsen MH, Specht L, Bentzen in mice. Journal of Labelled Compounds and Time Structured Light. I Image Analysis: 19th death of drug-resistant colorectal cancer cells. B M SM. Immunohistochemical biomarkers and Radiopharmaceuticals. 2015 May 30;58(6):227-33. Scandinavian Conference, SCIA 2015. 2015. 149-58. C Cancer. 2015;15:411. FDG uptake on PET/CT in head and neck Severin G, Jørgensen JT, Wiehr S, Rolle A-M, Hansen Wulff S, Pinborg LH, Svarer C, Jensen LT, Nielsen Persson M, Skovgaard D, Brandt-Larsen M, squamous cell carcinoma. Acta Oncologica. 2015 AE, Maurer A, Hasenberg M, Pichler B, Kjær A, MØ, Allerup P, Bak N, Rasmussen H, Frandsen Christensen C, Madsen J, Nielsen CH, Thurison Oct;54(9):1408-15. Jensen AI. The impact of weakly bound ⁸⁹Zr on E, Rostrup E, Glenthøj BY. Striatal D2/3 Binding T, Klausen TL, Holm S, Loft A, Berthelsen Revunov EV, Jørgensen JT, Jensen AI, Hansen AE, preclinical studies: non-specific accumulation in Potential Values in Drug-Naïve First-Episode AK, Ploug M, Pappot H, Brasso K, Kroman N, Severin G, Kjær A, Zhuravlev F. Automated solid tumors and aspergillus infection. Nuclear Schizophrenia Patients Correlate With Treatment Højgaard L, Kjær A. First-in-human uPAR PET: synthesis and PET evaluation of both enantiomers Medicine and Biology. 2015 Apr;42(4):360-8. Outcome. Schizophrenia Bulletin. 2015 Feb Imaging of Cancer Aggressiveness. Theranostics. of [¹⁸F]FMISO. Nuclear Medicine and Biology. 2015 Severin G, Nielsen CH, Jensen AI, Fonslet J, Kjær A, 18;41(5):1143-52. 2015;5(12):1303-16. Apr;42(4):413-9. Zhuravlev F. Bringing Radiotracing to Titanium- Ye Y-X, Calcagno C, Binderup T, Courties G, Keliher

66 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 67 SpinLab MR Hyperpolarizer

Example of hyperpolarized MRS in a dog with thyroid cancer. Lactate and The hyperpolarized Pyruvate is drawn into a vial. Alanine is produced from the injected hyperpolarized Pyruvate, as a result The PET/MR scanner is right behind the hatch. of the shift to aerobic glycolysis in the cancer (Warburg effect).

Andreas Kjær and Adam Espe Hansen

In 2014 the department was the first worldwide When a hyperpolarized compound like improving, we have a strong basis for future to have a combined PET/MR system with a 13C-Pyruvate is then injected, its conversion to human studies. MR hyperpolarizer installed. 13C-Lactate can be followed in real time. As of the end of 2015 more than 70 animal Through hyperpolarization the signal from The system is integrated with quality control studies have been performed in canines, pigs 13C-compounds, e.g. 13C-pyruvated to study and can hyperpolarize 4 samples at the same and rodents by us. The biological compound, metabolism, is made 10,000 to 100,000 fold time. The system is operated by specially which has been used so far is Carbon-13 en- higher. The hyperpolarization is obtained by a trained PET technologists. The technologists riched Pyruvate. In all studies an MR signal combination of low temperature (1 K), a mag- have been able to obtain a success rate for from the injected Pyruvate has been detected, netic field og 4 Tesla and irradiation by micro sample production of 87 % during the first along with one or more metabolites generated waves. 1½ years of operation. With procedures still in real time.

68 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 69 HyperPET

HyperPET with combined 18F-FDG-PET and 13C-Lactate-MRSI performed in the dog Fiola (32 kg) with a sarcoma on the right forepaw. Andreas Kjær and Adam Espe Hansen Coronal image (left) shows location of tumor and slice section for MRSI. Axial images (right) show 18F-FDG-PET and 13C-Lactate-MRSI.

Since installation of the SpinLab MR hyperpolarizer system in proximity to the PET/MR scanner on March 25, 2014, more than 70 animal studies have been performed in canines, pigs and rodents.

In 2014 we performed the first scan using simultaneous combined hyperpolarized MR and PET. Since then, continued studies have shown in a series of canine cancer patients that hyperPET, a name given by us to the combined technique, is feasible and can easily be performed within 2 hours. We showed a rough correspondence between 13C-lactate production 18 and F-FDG uptake and expect the combined Example of HyperPET with combined 18F-FDG-PET and modalities to reveal additional metabolic in- 13C-Lactate-MRSI performed in a dog (39 kg) with a sarcoma in the formation to improve prognostic value and axilla. FDG uptake and lactate generation is observed both in the tumor improve response monitoring. and a proximal lymph node.

70 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 71 Research

Andreas Kjær

A continuous focus on research and develop- coefficient (ADC) and magnetic resonance Clinical PET/CT in oncology Integrated Molecular Brain Imaging, neurore- ment is a keystone of the department. Over the spectroscopy (MRS). Most recently, the use of A large number of prospective protocols are ceptor ligands have been developed and used years, we have developed a comprehensive PET/MRI for radiation therapy is being eva- undertaken to evaluate the diagnostic and for research in neurobiology. The focus has research program with strong national and in- luated. With access also to preclinical PET and prognostic value of PET/CT with different trac- mainly been on the serotonergic system. ternational collaborations. We constantly adjust MRI, we are capable of working translational ers, including our in-house developed ones, in our research program to develop solutions to when developing and evaluating new methods. various forms of cancer both in children and in Functional MR health challenges in patients. Particularly, our adults. Head-to-head comparison studies of new With focus on the brain and in collaboration research program focuses on development of Hyperpolarized 13C-MRSI PET tracers and established imaging methods with clinical departments including neurology new tracers for PET, PET/MRI hybrid imaging, With the installation of equipment for dynamic are also performed. The use of PET/CT for the and psychiatry, development of new methods theranostics, clinical evaluation of new diagnos- nuclear polarization of 13C-labeled compound, planning of radiation therapy (“dose-paint- for functional MRI and clinical application of tic methods, and on the use of methods from e.g. 13C-pyruvate we have developed a research ing”) and the use of respiratory gating are new functional and molecular MR methods clinical physiology and nuclear medicine to program with focus on the use of this technique also currently being evaluated. Many of these are pursued. Methods are targeted at obtaining study pathophysiology. Translational research for tissue characterization in cancer and cardio- studies also now include PET/MRI to study the information on tissue physiology, organ perfu- in molecular imaging is given special attention vascular disease, but not limited to these areas. added value compared to PET/CT. sion and molecular biology. in order to accelerate translation of new tracers Since the system is the first in the World that into clinical use in patients. Current major re- Figure showing first-in-humans uPAR-PET/CT imaging in a patient is installed next to a PET/MRI scanner, special Paediatric nuclear medicine investigations Atherosclerosis search areas, many of which are seeking to ful- with prostate cancer using the PET tracer 64Cu-DOTA-AE105. attention is given to how the combination of hy- The department conducts many paediatric With the use of PET/CT and PET/MRI we can fill unmet patient needs, are mentioned below perpolarized 13C-MRS and PET can be combined investigations. Several research protocols with non-invasively visualize atherosclerosis and in what we have named hyperPET. We have the use of PET and SPECT are carried out in probably predict vulnerability of atherosclerotic New tracers demonstrated not only that hyperPET is feasible cooperation with clinical departments, par- plaques. With this technique, several studies in Numerous ongoing projects are aimed at deve- in several cancer forms. We have developed a expanded our research program on this topic but when performed with FDG and 13C-Pyru- ticularly within oncology and function of the different groups of patients at risk and with the lopment of new, specific tracers for non-invasive comprehensive platform for validation of new with focus on the added value of combining vate it can discriminate the Warburg effect from hepato-biliary system. The use of PET/MRI in use of new PET tracers are currently undertaken. tissue characterization. These tracers are to tracers including cell laboratory, molecular PET and MRI. With the aim of unfolding the other causes of increased glucose uptake. This is children to save radiation dose is also the sub- The goal is to develop an image-based algorithm be used for the diagnosis of different cancer biology (proteomics and genomics), histology full potential of PET/MRI through combining a most powerful, non-invasive tool for the study ject of investigations. for identification of patients at risk that will benefit types as well as for planning and monitoring of and biomarker laboratory facilities at the de- PET molecular imaging and MRI multipara- of metabolism in cancer and other pathological from surgery. Since we as the first published thera-py. The projects, which are translational partment. We currently have several promising metric imaging a large number of clinical trials conditions. Currently other PET tracers are com- Neuro PET data showing advantages of PET/MRI over in nature, are carried out in collaboration with new PET tracers in our developmental pipeline as well as projects on method development are bined with hyperpolarized 13C-MRSI to evaluate With the use of PET/CT, including HRRT, studies PET/CT for carotid artery imaging we have con- other departments and laboratories both nation- and expect several of these to be translated into currently undertaken. The focus is on the com- which combinations may hold valuable clinical on brain tumors are undertaken. Studies of tinued to develop vascular imaging using ally and internionally. A recent example of such clinical use within the next years. bined use of the modalities for improved tissue information. Our goal is to develop methods brain perfusion using PET or DCE-CT are also PET/MRI with special focus on new PET tracers. new tracer developed at the department is the characterization and response monitoring in that through use of the combined modalities, are performed. In addition, imaging of dementia first PET tracer to visualize the invasive cancer PET/MRI cancer treatment, paediatric studies, brain studies superior in cancer phenotyping and therapy with new tracers and brain tumors with FET Nuclear cardiology phenotype based on uPAR targeting. This tracer, Being one of the first centers to have an inte- and atherosclerotic plaque characterization. monitoring with the intention of providing is studied. PET/MRI is now fully integrated With the ability to measure absolute coronary 64Cu-DOTA-AE105, was recently taken into grated PET/MRI scanner installed, we have Focus on MRI includes the use of diffusion better tools for tailoring therapy. Like in other of into many of these studies. In cooperation with flow and myocardial perfusion by82 Rb PET, first-in-humans and showed promising results over the years continuously developed and weighted images (DWI) / apparent diffusion our research fields, our approach is translational. Neurobiology Research Unit and Centre for several studies on the regulation of these pa-

72 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 73 BIIC

Malene Fischer

rameters are undertaken. Studies include the Studies of muscle function or alpha-emitting radionuclides. Cancers that BIIC is an acronym for Better Imaging in In- generates highly complex datasets and an im- effect of various cardiovascular diseases and Using methods from clinical physiology and are currently being targeted clinically include flammation and Cancer. BIIC might sound big, portant part of this study is to test and validate the influence of interventions including gene nuclear medicine as well as molecular analyses, neuroendocrine tumors and ovarian cancer. but denotes a small albeit growing research different methods for integrating data from therapy, pharmacological treatment and exer- muscle function, bone density and body com- Treatment with radionuclides will in part be group centred on a portfolio of clinical research multi-parametric and multi-time point imag- cise. With the use of SPECT/CT or PET/CT position are studied with focus on the effect based on imaging using new tracers for molecu- projects. These projects aim to increase our ing. This is done in close collaboration with the development of ischaemic heart diseases of exercise, immobilization and ageing. Also, lar profiling or the same ligand as the therapy understanding of the intersection between in- PET/MR physicist and engineers. The first is studied in selected groups of patients, e.g. data are collected on these parameters from a (theranostics) for better outcome and fewer flammation and cancer in an imaging perspec- preliminary results on the analysis of multi- HIV and hepatitis patients. On basis of this, population-based study. These data will serve side effects. The concept of a tracer that visuali- tive. All projects are based on a close collabo- parametric imaging where presented at screening algorithms for detection of ischae- as a reference database and elucidate markers zes the target prior to starting therapy is also ration with our clinical colleagues, especially EANM in 2015 as an oral presentation. mic heart disease are evaluated. Some of the to predict aging-related disease. known as companion diagnostics. the departments of Oncology and Infectious studies are combined with PET tracers charac- Diseases, as well as the MATCH (Managing In 2015 BIIC received funding from the terizing other aspects of the myocardium and Inflammation, infection and rejection Image guided surgery of Post-Transplant Infections in Collaborating Danish Cancer Society “Knæk Cancer” its viability. Several of the studies are per- Research with non-invasive imaging of in- Intraoperative guidance using either radio- Hospitals) and the PERSIMUNE collaboration. and the Michaelsen Foundation. formed using PET/MRI to obtain additional flammation and infection is currently being active or optical imaging ligands is increasingly Both contributions are highly information. undertaken at the department. Also studies on used for surgery. In collaboration with clinical In short, BIIC examines the inflammation-can- appreciated and a prerequisite for how rejection reactions can be visualized and departments we have recently developed one cer intersection in two main areas: First, inflam- our continuing research. Lung studies evaluated are now performed. In some studies, of our most promising PET ligands targeting mation as a predisposing factor, increasing the Research using lung function testing the added value of MR-derived parameters of uPAR into an optical probe. This probe will be risk of cancer. To this end we examine the use and lung scintigraphy in different patient PET/MR is studied. The department is partner used for intraoperative delineation of cancer to of PET/CT and PET/MR for detection of focal groups, e.g. lung transplantation and en- in the PERSIMUNE program, personalized ensure free margins while leaving normal tis- inflammation/infection and early detection of dobronchial stenting for emphysema, are medicine of infection complications in immune sue intact. The technology, which will be used cancer. Second, inflammation induced during undertaken. The value of combined use of deficiency. Finally, on a translational basis de- in pair with preoperative PET imaging of the or after therapy, e.g. flare during chemotherapy SPECT/CT for diagnosing pulmonary embo- velopment of new PET ligands for immune re- same target, is particularly promising in con- and inflammation after radiotherapy, hamper- lism has recently been evaluated. The value sponse monitoring is currently being pursued. cert with robotic surgery. ing our ability to perform early therapy evalu- of biomarkers in combination with imaging ation and detection of relapse. The latter is is also studied. In addition, evaluation of the Radionuclide treatment and theranostics Whole body counting explored in an on-going clinical trial comparing different ventilation tracers for assessment Localized radiation therapy using beta- or alpha- Together with external partners, whole body FDG and FLT-PET. of ventilation inhomogeneity is undertaken. emitting specific ligands binding to certain counting is used for exact measurements of Research is also being conducted into muco- cancer forms has been undertaken for several body composition in a series of studies. In In the WHEN study we explore whether ciliary clearance, a method pioneered at the years at the department. The department takes addition we are investigating absorption of cer- PET/MR with FDG and DWI performed be- department, of the nose and lungs. Finally, part in research within this area by testing new tain minerals from the gastrointestinal tract. fore, during (up to 3 times) and after the first the department is participating in a large ligands and producing relevant isotopes. We cycle of chemotherapy can discriminate be- study colleting data for a lung function test also develop several new theranostics based on tween therapy induced inflammation, tumor reference database. promising imaging ligands labeled with beta- response and lack of response. This study

74 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 75 Cluster for Molecular Imaging

The “translational bridge” with our key competencies highlighted in grey Andreas Kjær

The paradigm of precision medicine, i.e. tailor- Our current molecular imaging and theranos- p Radioactive labelling of ligands currently several new tracers in pre-clinical scheduled for cancer therapy. The latter allows Currently the main focus of the translational re- ing therapy to the individual characteristics of tics research program is aimed at through use p Test of imaging ligands in relevant animal testing in animal models that already have or for testing in “full-size” as well as evalu- search in tracers for non-invasive tissue charac- each patient, has led to a need for diagnosing at of molecular biology and imaging techniques models soon will become available for human use. A ation of tumor-stroma interaction due to the terization is on the use in cancer and cardio- the molecular level. Molecular biology methods in both animals and humans to develop, evalu- p Use of imaging data for therapy planning strong focus has recently been on the use of syngeneic tumor environment. In this way we vascular disease and new targeted radionuclide need tissue sampling for in vitro analysis. In ate and use non-invasive molecular imaging for and monitoring of response in animal more clinically relevant animal cancer models, bridge between xenograft models and first-in- therapies for cancer. However, we also perform contrast, molecular imaging allows for whole- human tissue characterization. Major applica- models which include orthotopic human xenograft human studies. studies within molecular imaging of inflamma- body non-invasive studies at the molecular level tions of these tracers are expected to be: p Use for diagnosing, therapy planning and tumors as well as metastatic cancer models tion and metabolism, e.g. activation of brown in intact organisms circumventing sampling 1) planning of individualized, tailored therapy, monitoring in patients using human cancer cell lines. Most recently, At Cluster for Molecular Imaging we always adipose tissue. error. It is possible to label almost any molecule 2) testing of new drug candidates and 3) basis p Use for testing of new drugs we also implemented the use of patient- seek to match our clinical methods to be with radioactive isotopes suitable for PET im- for development of radionuclide therapy (ther- p Use as starting point for new targeted derived tumors (PDX) for orthotopic implan- able to develop new techniques for use in Some tissue characteristics currently targeted aging. Such molecular imaging ligands can be anostics). therapies, in particular radionuclide based tation to even better mimic the conditions in patients. Accordingly, we have most recently for imaging: used for visualization of tumor specific recep- therapies cancer patients. Furthermore, we have also added SPECT/CT capabilities to our existing p Cancer specific eceptorsr (numerous pro- tors and tissue characteristics such as angio- The development of new molecular imaging introduced and developed animal models of PET/MRI/MRS capabilities. SPECT/CT jects, e.g. SST and HER2) genesis and ability to metastasize. Especially tracers for PET is a very complex process that Through establishment in 2003 of Cluster for cardiovascular diseases including atheroscle- will in particular be used to visualize p Glycolytic activity (PET and hyperpolarized within cancer biology the technique is expected involves many steps from definition of target to Molecular Imaging at the Faculty of Health and rosis, myocardial infarction and takotsubo. For 177Lu-labeled radionuclide therapy ligands MRSI) to lead to a break-through in diagnosing and final use of the tracer in patients. Medical Sciences, University of Copenhagen studies of atherosclerosis also mini pigs and to investigate biodistribution and binding p Cell proliferation treatment. Among the different techniques for (headed by Professor Andreas Kjær) a speciali- rabbits are used. to tumors. Also, we currently perform pre- p Amino acid transport molecular imaging, the nuclear medicine based Major steps involved in PET tracer zed facility at the Panum Institute for molecular clinical studies in the field of hyperpolarized p Hypoxia technologies have the greatest translational po- development and translation into patients imaging in animals with PET, SPECT, CT, MRI Over the last years 10 years we have build a 13C-MRS in collaboration with Hvidovre Hos- p Apoptosis tential as they can be directly transferred from p Selection of key-processes involved in the and optical imaging has been established. This translational platform for development of new pital and DTU. Recently, also optical imaging p Angiogenesis animal models to use in humans. In addition, pathophysiology of the disease has improved our translational capacity since PET tracers in cancer. The platform includes, af- has gained translational potential as it can p Invasive cancer phenotype successful imaging ligands may be developed p Definition of elevantr molecular targets of we are now able to test new tracers and radio- ter testing in orthotopic human xenograft tum- be used intraoperatively for delineation of p Atherosclerotic plaque vulnerability into radionuclide therapy, such an imaging- the key-processes nuclide therapies in animal models prior to ors in mice, early use of promising PET tracers tumors. p Immune-response therapy pair is known as theranostics. p Design of specific ligands clinical use. In accordance with this we have in companion dogs with spontaneous tumors

76 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 77 Collaboration with Landssygehuset, Faroe Islands

Jann Mortensen and Thomas Levin Klausen

The Department of Clinical Physiology, Nuclear (511 in 2014) scintigraphies of lungs, bones, Medicine & PET, Rigshospitalet has a close thyroid, kidneys, sentinel nodes and reno- collaboration with Landssygehuset in Tórshavn, graphy in 2015 on the department´s 2-headed Faroe Islands. Skylight camera. A total of 425 (627 in 2014) lung functions test were performed with the The hospital has a staff of 850 and 160 beds. Jaeger whole body plethysmograph. The Nor- The 8,000 in-patients and 60,000 out-patients land DXA 840 scanner has been used for a total annually are taken care of by 29 specialities, of of 470 (410 in 2014) routine and reseach studies. which 9 are via consultant collaborations, Second opinion on scintigraphy and lung including collaboration with Clinical Physiology function measurements is provided via a direct and Nuclear Medicine, Rigshospitalet. telemedicine connection. The responsible physician and phycisist for Nuclear Medicine in The Department of Clinical Physiology and Tórshavn is Consultant, DMSc Jann Mortensen Nuclear Medicine in Tórshavn performed 452 and Physicist Thomas Levin Klausen.

78 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 79 Danish-Chinese and Danish-Indian Research Collaborations

Danish-Chinese Centre for Proteases and Cancer The Danish National Research Foundation and The National Natural Science Foundation of China

In 2015 the Department continued its collaboration with leading In addition to Rigshospitalet, the partners are Aarhus Uni- research institutions in China through the Danish-Chinese versity, Chinese Academy of Sciences, Fuzhou and Soochow Centre for Proteases and Cancer where Professor Andreas University, Suzhou. Kjær is senior partner. The Centre is funded by the Danish National Research Foundation (Danmarks Grundforsknings- Also with India, we continued our collaboration in 2015 with fond) and the National Natural Science Foundation of China. Professor Abhijit De from the Advanced Centre for Treat- ment, Research and Education in Cancer (ACTREC) of the The main focus of the Centre is to perform research that Tata Memorial Centre and Hospital in Navi Mumbai, the amongst other applications should lead to new molecular largest cancer hospital in Asia. The collaboration continues imaging ligands and tailored therapies. Our focus has to work on development of new and cost-effective methods throughout been development of new PET imaging ligands for targeted radionuclide therapy in patients with breast to identify the invasive cancer phenotype and their trans- cancer. Currently, also the potential of using alpha-emitters is lation into clinical use. It is with proud that we have in 2015, pursued. Experimental work is undertaken both in India and the last year the Centre is funded, reached our goal of clinical Denmark. testing of uPAR-PET. 80 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 81 PhD degree in medical and Global Academic Program molecular imaging MD Anderson’s Sister Institution Network

Consultant Annika Loft Jakobsen and Professor Andreas Kjær presented clinical data on two new PET tracers developed at our department at the 2015 GAP Conference.

The research at our department involves numerous PhD the PhD students presented their projects with the aim of In 2014 Rigshospitalet was selected as the first Danish of the Sister Institution Network. The event is held at MD students. These PhD students are enrolled in the PhD pro- generating new ideas and invite to collaborations across dis- institution to become a sister institution of MD Anderson Anderson in odd years and is hosted by a Sister Institution in gram for Medical and Molecular Imaging at the Faculty of ciplines and departments. In addition, affiliated professors Cancer Center and be part of the Global Academic even years. Health and Medical Sciences, University of Copenhagen. and senior researchers gave lectures on subjects of general Programs (GAP). GAP facilitates and administers MD The program was established in 2010 in acknowledgment of interest, e.g. why scientific articles get rejected (editors Anderson’s Sister Institution Network, which is the largest Accordingly, in 2015 the GAP Conference was held at MD the ever-increasing research field of medical and molecular view), how to attend conferences, web-based imaging tools global network of cancer centers working collaboratively Anderson Cancer Center in Houston, TX. From Rigshospitalet imaging. Professor Andreas Kjaer heads the program. The and regulatory issues. on research and education aimed at lessening the world’s a delegation of 10 persons, headed by Medical Director Jannik program offers PhD courses covering both technical aspects cancer burden. Hilsted, participated in the conference. Our department was of PET, CT, MRI and optical imaging as well as disease ori- In 2015 a total of 11 PhD students from our department were represented by Consultant Annika Loft Jakobsen and Professor ented courses in imaging, e.g. imaging in oncology. granted the PhD degree. The majority of these were enrolled Each year, a GAP Conference is held to provide a forum for Andreas Kjær. They presented clinical data on two new PET in the PhD program for Medical and Molecular Imaging. faculty from MD Anderson and Sister Institutions to develop tracers, which were developed at our department. During the In 2015 a two-day workshop for enrolled PhD students of collaborations and exchange research results and ideas. conference fruitful discussions on future collaborative projects the program was held in Helsingør. During the workshop Sessions are formed around topics of interest to the members were discussed and organized.

82 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 83 Young Investigator Prizes 64Cu-DOTATATE PET

Prospective study of 112 neuroendocrine tumor patients Awardee Karina Juhl published in the Journal of Nuclear Medicine together with Dr. Anders Christensen and Professor Andreas Kjaer at the WMIC conference.

Andreas Kjær

The 2015 Lundbeck were encouraging with substantially more foci detected by 64 111 Foundation Clinical Cu-DOTATATE compared to In-DTPA-octreotide. Research Fellowship awardees. Mathias This led us to initiate a larger prospective study enrolling Dyrberg Loft is 112 patients over more than one year. All patients underwent number 2 from right. both a 64Cu-DOTATATE PET/CT and an 111In-DTPA-octreotide SPECT/CT scan to allow for head-to-head comparison. Follow-up was undertaken for 42-60 months to determine if discrepant findings could be categorized as true or false.

In brief we found that patient-based, 64Cu-DOTATATE PET/CT had a higher diagnostic sensitivity and accuracy than 111 PhD student Ingrid Holst Olsen (joint with Dept. of Postdoc Morten Persson: International Best Abstract Award Results from the prospective study using In-DTPA-octreotide SPECT/CT. Lesion-based, more than 64 Endocrinology, Abdominal Surgery, Oncology and at the annual meeting of the Society of Nuclear Medicine and 64Cu-DOTATATE PET/CT in 112 neuroendocrine tumor patients twice as many foci were identified by Cu-DOTATATE 111 Pathology): Nordic Neuroendocrine Tumour Group Molecular Imaging (SNMMI), Baltimore, USA, June 2015: were presented by Professor Andreas Kjær as a plenary lecture at compared to In-DTPA-octreotide. Follow-up in general Scholarship for Young Researchers in Neuroendocrine Abstract: Persson M, Skovgaard D et al. Safety and dosimetry the 2015 Annual Meeting of ENETS in Barcelona, Spain. proved most of the additional lesions detected only by Tumors, Stockholm, Sweden, October 2015. Project of first-in-humans uPAR PET imaging. 64Cu-DOTATATE to be true positive and none were false title: Nordic study on the impact of surgery on patients positive. with gastroenteropancreatic neuroendocrine carcinomas Medical student Mathias (GEP-NECs). Characterization of GEP-NECs by imaging, Dyrberg Loft from our As part of our program for development of new PET tracers, The study was published in the Journal of Nuclear Medicine immunohistochemistry and qPCR. department was awarded a one- we published in 2012 first-in-humans data from 14 patients in 2015 and presented as a plenary lecture at the European year Lundbeck Foundation Clinical Research Fellowship using 64Cu-DOTATATE, a new PET tracer for neuroendocrine Neuroendocrine Tumor Society (ENETS) annual meeting in Research assistant Karina Juhl: Student Travel Stipend Program stipend to perform a joint project at Stanford tumors targeting somatostatin receptors. Barcelona, Spain. Award based on abstract score. World Molecular Imaging University. Project title: Plasma PSA and uPAR PET imaging Congress, Honolulu, USA, September 2015. Abstract: Juhl K, for early Identification of Invasive Prostate Cancer Phenotypes The advantages of 64Cu-DOTATATE include low-energy The development and testing of the new tracer was headed by Christensen A et al. Delineation of tumor margins in vivo with (co-supervisors: Assoc. Professor Zhen Cheng and Professor positrons and a physical half-life of 13 hours. These proper- Professor Andreas Kjær and undertaken as a multidisciplinary a uPAR-targeted NIR optical imaging probe, using the fluorophor Andreas Kjær). ties translate into a high spatial resolution and a wide time- collaboration within the European Center of Excellence for Neu- indocyanine green. frame for image acquisition. Results from these first patients roendocrine Tumors at Rigshospitalet and with DTU.

84 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 85 CIMBI Professor Liselotte Højgaard received: ”Chevalier d’lordre de la legion d’honnour” from the French ambassador to Denmark, Francois Zimeray Center for Integrated Molecular Brain Imaging, University of Copenhagen, Rigshospitalet

We appreciate the excellent collaboration with Professor The focus of the research program is neurobiology, Gitte Moos Knudsen, Chair of the Neurobiology Research physiology and pathophsiology, molecular imaging and Unit at Rigshospitalet, University of Copenhagen and also neuroreceptor ligands with focus on the serotonergic system. Director of the CIMBI, Center for Integrated Molecular Brain Imaging. https://cimbi.dk/

86 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 87 MSc in Medicine and Technology

Liselotte Højgaard

In cooperation with the Technical University of and we have numerous students working with Denmark (DTU) and the University of Copen- bachelor and master reports in collaboration hagen (KU), the Department represented by with DTU, IMM (Institute for Mathematical Professor Liselotte Højgaard is involved in the Modelling), Professor Rasmus Larsen and DTU, MSc program in Medicine and Technology. It is Electro with Professor Jørgen Arendt Jensen. a five year bioengineering degreee at bachelor A warm thank you to Professor Jørgen Arendt and master level. The first masters graduated in Jensen, Associate Professor Kaj-Åge Henneberg, 2008. You can read more about the program at Professor Jens E. Wilhjelm, DTU and Associate www. medicin-ing.dk. Professor Bente Stallknecht and Associate Professor Tine Alkjær Eriksen, University of At present several of these bioengineers are Copenhagen, for their great effort and our fine seconded to the department as PhD students collaboration both on education and research.

88 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 89 Danish National Research Foundation © René Magritte / Billedkunst.dk

Professor Liselotte Højgaard is Chair of the professorships. Since 1991 the Foundation has new generation of 12 centers are up and run- Board of the Danish National Research Foun- commited itself to support Danish Research ning by the 1st of January 2015 as a result of dation. The board members are end 2015: with more than 6 billion DKK (≈ 800 mio €). the 8th application round. The DNRF also has Professor Liselotte Højgaard, Professor Eivind the Niels Bohr professorships. Hiis Hauge, Professor Eero Vuorio, Professor The Center of Excellence is the primary fund- Dr. Bart De Moor, Professor Chistina Moberg, ing mechanism and the Foundations’ flagship. A In 2013 DNRF was evaluated by an inter- Professor Morten Overgaard Ravn, Professor center grant is large and flexible, and a center national panel leader by Dr. Wilhelm Krull, Minik Rosing, Professor Jesper Ryberg and may have a lifetime up to 10 years. Only top Secretary General of Die Volkswagen Stiftung. Professor Anne Scott Sørensen. researchers with the most ambitious ideas The outcome was very positive and showed will be awarded a CoE through fierce com- that the DNRF CoE’s are on level with the The Danish National Research Foundation petition involving af two-stage application very best researches in the world. The out- (DNRF) is an independent organisation esta- process. The objective of the CoE program is come was very positive, and a continuation blished by the Danish Parliament in 1991 with to strengthen Danish research by providing of DNRF was recommended to the Danish the objective to promote and stimulate basic the best possible working conditions and or- Parliament and Government. The Danish Par- research at the highest international level at ganisational setup for selected top researchers. liament gave the Foundation 3 bio DKK on the the frontiers of all scientific fields. The Center Centers may be established within or across State Budget for 2015 to secure the Foundation of Excellence (DoE) program is the main fund- all fields of research. A total of 100 Centers of to 2036. ing mechanism together with the Niels Bohr Excellence have been established so far, and a

90 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET 91 Editors Liselotte Højgaard Accreditation Vibeke Rønn

Layout Eckardt ApS

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Photos Tomas Bertelsen Steen Brogaard Büro Jantzen Andreas Kjær Joachim Rode Esben Salling Ty Stange

Issues 1000 ex.

Copyright Department of Clinical Physiology, Nuclear Medicine & PET Rigshospitalet University of Copenhagen Blegdamsvej 9 DK 2100 Copenhagen Ø Denmark

Contact Rigshospitalet and our department have been accredited succesfully by: Professor Liselotte Højgaard E-mail: [email protected] » Center of Excellence by the European Neuroendocrine Tumor Society Phone: +45 3545 4215 » Certified by SIS, National Institute of Radiation Protection, The Danish National Board of Health » Danish Medicines Agency » The Danish National Board of Health, MD Specialist education » EURATOM, The European Atomic Energy Community » Section of Nuclear Medicine of the European Union of Medical Specialists (UEMS) » Accreditation of Nuclear Medicine Training Centers Committee, MD Specialist Education » European Association of Nuclear Medicine » The Specialty Advisory Committee (SFR) in Clinical Physiology and Nuclear Medicine

92 Department of Clinical Physiology, Nuclear Medicine & PET Department of Clinical Physiology, Nuclear Medicine & PET Rigshospitalet, KF Section 4011 Blegdamsvej 9 2100 Copenhagen Ø, Denmark Telephone: +45 3545 4011 Fax no: +45 3545 4015 Mail: [email protected]

Department of Clinical Physiology, Nuclear Medicine & PET Rigshospitalet, PET Section 3982 Blegdamsvej 9 2100 Copenhagen Ø, Denmark Telephone: +45 3545 3919 Fax no: +45 3545 3898 Mail: [email protected]

Department of Clinical Physiology, Nuclear Medicine & PET Rigshospitalet, Glostrup Section Nordre Ringvej 57 Entrance 1, 2nd floor 2600 Glostrup Telephone: +45 3863 2434 Fax no: +45 3863 3928 Mail: [email protected]

www.rigshospitalet.dk/afdelinger-og-klinikker/ diagnostisk/klinik-for-klinisk-fysiologi-nuklearmedicin-og-pet